MESENCHYMAL STEM CELL COMPOSITIONS AND METHODS OF MAKING

BACKGROUND
1. Field

The present invention relates to compositions comprising exosomes and extracellular matrix components and the use thereof.

2. Discussion of Related Art

Mesenchymal stem cells (MSCs) are highly proliferative, multipotent cells that can be isolated from tissues including umbilical cord, placenta, bone marrow, and fat and can differentiate into mesenchymal cell with negligible risk of teratoma formation. These cells secrete exosomes which are nano particles or extracellular vesicles of about 30 nm to −250 nm in diameter. Exosomes carry proteins, lipids, and nucleic acids (miRNA mRNA, ssDNA), loads from the cell, and as such, perform a functional role that mediates paracrine signaling, cellular-cell communication, trophic factor regulation and immunomodulation. They are also thought to play a role as biomarkers of certain disease models. Because exosomes are a form of “natural” drug delivery, and do not elicit acute immune rejection, they can be loaded ex vivo with certain therapeutic agents and targeted to deliver their therapeutic loads to specific cell types. In addition to exosomes, there are components normally encapsulated in an extracellular matrix (e.g., growth factors, signaling molecules) that can be useful as therapeutics. However, it is difficult to concentrate these components and isolate them from an intact cell culture and tissue sample. As an example, these useful components are often discarded in supernatant fractions when exosomes are prepared and purified using centrifugation.

Thus, methods of obtaining preparations of exosomes and components from that are homogenous, intact, free of contaminants, and concentrated enough to provide commercially viable and therapeutic yields are still needed.

SUMMARY

The present disclosure is based, at least in part, on the discovery and development of an exosome composition comprising (a) at least one exosome produced by a mesenchymal stem cell or fibroblast cell, (b) at least one component isolated from an extracellular matrix (an ECM component).

In various aspects, the at least one ECM component is selected from the group consisting of a glycosaminoglycan or proteoglycan thereof, an adhesive glycoprotein, a fibrous protein, a growth factor, a cytokine, a peptide, a nucleic acid, or a lipid. For example, in some embodiments, the at least one ECM component may comprise a glycosaminoglycan selected from the group consisting of hyaluronan, chondroitin sulfate (CS), dermatan sulfate (DS), keratan sulfate (KS), and heparan sulfate (HS), or any proteoglycan thereof. As another example, the at least one ECM component may comprise an adhesive glycoprotein selected from the group consisting of Laminin, Fibronectin, tenascin, and nidogen. As yet another example, the at least one ECM component may comprise a fibrous protein selected from the group consisting of collagens and elastin.

In further aspects, at least one ECM component comprises a growth factor selected from the group consisting of EGF, Endothelin, Eotaxin/CCL11, FGF-4, GDF-15, ICAM-1, IGFBP-1, IL-6, PDGF-AA, TGF-beta 3, TIMP-1, TIMP-2, BCAM, Smad 4, CD 163, CD30 Ligand, TNFSF8, and Integrin b1.

In other aspects, the at least one ECM component may be selected from the group consisting of Cysteine-rich Protein 1, PIM2, Cadherin-13, Beta IG-113, EG-VEGF/PK1, Cyclophilin A, Dkk-3, BMP-3, QDPR, PAM, EDAR, EGF R/ErbB1, ALCAM, CXCR3, SBP-1, BCMA/TNFRSF17, CCL28/VIC, IL-29, HSP47, VE-Cadherin, I-309, TGF-beta RIII, CCR8, Fractalkine, TCN1, RSU1, uPAR, VEGF-D, PRELP, TGF-beta RII, Thrombopoietin (TPO), Endothelin, S100A6, Angiogenin, TIMP-4, MSP alpha Chain, Activin A, DMGDH, Serpin B8, TRAIL R3/TNFRSF10C, CFHR5, Caspase-14, PRDX 1, FGF-12, CXCR5/BLR-1, Semaphorin 7A, SPINK7, NT-4, TNF RII/TNFRSF1B, 6Ckine, SerRS, Angiostatin, Angiopoietin-like Factor, B7-1/CD80, Protein C, Tcf20, TROY/TNFRSF19, EMAP-II, CSH1, TLR4, RPLP0, ErbB3, RPL11, PGK-1, FGF-16, Plakophilin 1, PRCP, RAGE, Insulin, TSR2, NT-3, USP14, VDAC1/Porin, Proteasome 20S a+b, M-CSF, IL-2, ICAM-1, NEDD8, PRG2, Insulysin/IDE, ICAM-2, MMP-1, Salivary alpha amylase/aAmylase, IL-17F, Galectin-1, Lymphotoxin beta/TNFSF3, TBCA, PREP, VAP-A, Utrophin, YB1, VAP-1, CFHR4, FGF-20, Cyclophilin B, RNASE4, SBSN, FGF R4, FGF-17, PGLS-C-t, Eotaxin-3/CCL26, RREB1, TMEM223, ADAMTS-15, Semenogelin II/SEMG2, C3a, RPL12, GDF8, IGF-II, RPS25, Follistatin-like 1, Smad 5, Notch-2, 1-TAC/CXCL11, TRANCE, MMP-3, uPA, WDR1, UQCRB, DR6/TNFRSF21, BMP-15, PSMA4, ErbB4, Gephyrin, beta-NGF, BMP-2, BMP-6, NAP-2, LECT2, FGF-13 1B, Reg3A, CD14, SHIP, RPL5, VEGF, IL-1 F5/FIL1delta, RPS28, TUBA6, Endostatin, MMP-9, CK-MB, CapG, IL-11, Ribonuclease A, Eotaxin-2/MPIF-2, GLO-1, TLR3, HGF, Sterol carrier protein 2/SCP2, Visfatin, SHC1, IL-18 R beta/AcPL, SIGLEC14, PRTN3, Contactin-1, CV-2/Crossveinless-2, EDG-1, CXCL14/BRAK, TIMP-3, Serpin A1, Annexin A1, TGM3, CXCR6, PGM1, Osteoprotegerin/TNFRSF11B, Coagulation Factor III/Tissue Factor, M-CSF R, MDC, FAM3B, MMP-11/Stromelysin-3, SCF R/CD117, TGF-beta 5, Titin, sFRP-3, IL-1 beta, HCC-4/CCL16, TRAIL/TNFSF10, Fascin, BNP, ADAMTS-13, PLOD1, FLRG, LDHA, LIF, YY1, NME3, ESAM, RPS19, EpCAM, TAGLN2, CXCL16, BTF3, Hemoglobin subunit beta/HBB, TRADD, Metavinculin, BDNF, Galectin-7, PPP2R4, FACX, PDZD2, IL-26, FGF-9, Fibrinogen-like 2, Plexin B2, Thrombomodulin, Dtk, TRAIL R2/DR5/TNFRSF10B, PNP, ANGPTL8, B7-H3, ACLP, Galectin-3, p73, IL-4, IL-13 R alpha 2, TOB2, Claudin-3, IL-8, VEGF-C, IGF-I SR, Tenascin X(1), LefBy-A, Thrombospondin-1, OSM R beta, SUCLG1, PDGF-AB, IL-6 R, IL-18 BPa, PGAM2, Cripto-1, FGF-23, GSTM1, TCAM-5, RPLI0, Ribonuclease Inhibitor, ARTS1, Periostin, UCH-L1, Zyxin, RPL10A, PDLIM5, IL-15 R alpha, FAM3C, Tropomyosin 3, LZTS1, LIGHT/TNFSF14, Osteoadherin(2), SHMT1, CCR9, TWEAK R/TNFRSF12, TPP1, ADAMTS-10, RCL, PCDH7, MIG, SPARC, SH3BGRL, Thrombospondin-4, UFM 1, Prostaglandin D Synthase/PTGDS, GPR-39, SPTBN1, BLVRB, RKIP, 4-1BB, Decorin, CRIM 1, PCSK9, STI1, IL-22 BP, VEGF R2 (KDR), Ficolin-2, CXCR4 (fusin), SIGIRR, IFN-beta, Cyclin D1, MIP-1a, RPS11, Alpha 1 AG, BLAME, Cystatin E/M, GM-CSF R alpha, Uteroglobin(1), Trypsinogeb-2, MCP-3, Erythropoietin R, Proteasome subunit alpha type 6/PSMA6, TGF-alpha, Flt-3 Ligand, Nanog, TNF-alpha, Spectrin beta-5, VNN1, BMP-1, FGF-7/KGF, OSM, FGF R5, Transferrin, C5/CSa, ApoA1, TCP1 eta, Galectin-3BP, PTPRZ, TRAIL R1/DR4/TNFRSF10A, Six3, SORD, CNTF, GDNF, BMPR-II, CXCR2/IL-8 RB, FGF-8, RPS5, CRF21, PGDF/PHGDH, FABP1, SLURP1, CEACAM-8/CD66b, UNC45A, Adiponectin/Acrp30, MMP-25/MT6-MMP, SMC4, Ornithine Carbamoyltransferase/OTC, IFN-gamma R1, CCR4, Proteasome beta 1, Talin1&2, Prohibitin, MMP-24/MT5-MMP, SP-D, Nidogen-2, PTPRS, SIRP beta 1/CD172b, APRIL, ACE-2, IL-6, HGFA, E-Selectin, GATA-4, VEGF R3, UBE2D3, BAFF R/TNFRSF13C, Layilin, Cytokeratin 8, Profilin 1, Cathepsin B, Marapsin, Lymphotactin/XCL1, Nidgen-1, MEP1A, MIF, IL-1 F8/FIL1 eta, MMP-14, HB-EGF, Latent TGF-beta bp1, C8B, SMPD4, ADAMTS-18, FGF Basic, IL-12 R beta 2, MINPP1, URP2, Glycoprotein V, LRG1, ACPP, AlphaA Crystallin/CRYAA, EDA-A2, SH3BGRL3, Serpin F2, CD40 Ligand/TNFSF5/CD154, CPEB3, A2M, Activin B, SREC-II, EGF, FGF-19, Myoferlin, Endoglin/CD105, RECK, ADAM-9, SSEA-4, DDAH1, P-Cadherin, IL-22 R, Glut1, Symplekin, S100A11, SLITRK1, GCP-2/CXCL6, SDPR, IGF-II R, P4HB, TNF-beta, IL-1 R8, IL-1 alpha, Angiopoietin-4, TCCR/WSX-1, GITR/TNFRF18, ILK, TCEB2, RPL22, DEP-1, FGF-18, TLIA/TNFSF15, EphA6, IL-36RN, Tarc, UROC1, Activin C, FASN, PYGL, Somatostatin, Musk, PLA2GIB, IL-1 R3/IL-1 R AcP, FGF-6, IL-18 R alpha/IL-1 R5, Tie-2, NIT2, PF4/CXCL4, TPM1, GDF11, IGFBP-6, Thymopoietin, FUCA1, CRHBP, C1qR1, STAT3, TPM4, Follistatin, Laminin b2, IL-1 sRI, CCR7, ApoA2, ENA-78, Myosin 18B, Desmoplakin, Neurabin 1, FGF-4, PDGF-BB, PCBP2, P20Sb3, IGF2BP1, Chordin-Like 2, UNC-13 Homolog D, Enolase 2, Angiopoietin-2, TFF2(1), RHOC, SUMO3, DGK, HVEM/TNFRSF14, GRO-a, GALNT2, TECK/CCL25, Notch-1, Cystatin S, IL-2 R alpha, WNK2, eIFSA, TrypsinPan, SCF, CD30/TNFRSF8, IL-1 F6/FIL1 epsilon, CutA, CFL1, TRAIL R4/TNFRSF10D, MBD2, UBE2N/Ubc13, PI 16, DANCE, FABP2, IGFBP-4, NEP, NRG1 Isoform GGF2, IL-2 R gamma, MAC-1, MPO, SerpinE2, GDF1, IL-17, Orexin A, Kremen-1, Smad 4, IL-17B R, GCSF, Annexin V, IL-31, TRAP1, Transketolase/TALDO, pIgR, Brg1, BMX, MAN1, Orosomucoid 2, RAPIAB, VEGF-B, SLC38A10, RPS2, RANTES, SerpinB4, Nestin, Complement factor H, MAPRE1, PDGF-AA, Reg1A, MUCDHL, SSTR2, IGSF4B, TSG-6, Orexin B, Quiescin Q6, IGFBP-2, IGFBP-rp1/IGFBP-7, Dystroglycan, Alanine Transaminase/ALT, FKBP12, Growth Hormone R (GHR), MCP-1, IL-21, RANK/TNFRSF11A, HRG-beta 1, ACTC1, Ribonuclease T2, B3GNT1, Src(1), PCYOX1, Leptin R, IL-19, CXCR1/IL-8 RA, PTP mu, IL-1 ra, PDGF-D, HEXB, ERp57, PLC-gamma 1, Nesprin2, Frizzled-4, B7-H2, NAGLU, Serpin B5, TNF RI/TNFRSF1A, IL-1 F9/IL-1 H1, Histone H2B K, OX40 Ligand/TNFSF4, Aminoacylase, Transaldolase 1/TALDO1, Glucagon, IFRD1, sFRP-4, IL-22, Kininostatin/kininogen, PRDM13, CCR5, C1q, AMPKa1, EXTL2, POR, Smad 8, TXNDC5, IL-17RD, TREM-1, SDNSF, FKBP51, Complement Factor B, Cadherin-6, VCAM-1 (CD106), 11b-HSD1, Tie-1, Vimentin B, DISC 1, RPL7A, GDF-15, IL-31 RA, IL-5 R alpha, p16 ARC, EN-RAGE, Biglycan, DSCAM, Aggrecan, DCI, Cathepsin A, HGFR, sFRP-1, IL-4 R, IL-5, FGF R3, Activin RIA/ALK-2, Prdx6, Cathepsin L, Ezrin, TAX1BP3, FGF-BP, AMICA, KMD4B, Artemin, Axl, Claudin-4, SDF-1/CXCL12, FADD, MAP1A, ABCF1, Annexin A6, G-CSF R/CD 114, TSLP R, BRCA 2, EphA2, Cystatin SN, Fas Ligand, Pappalysin-1, ME1, 2B4, Fc RIIB/C, Dkk-4, alpha-Synuclein, Neural Cadherin, ANGPTL3, C1q S, ATBF1/ZFHX3, IGF-I, IL-3, IL-3 R alpha, Semaphorin 6B, DPPIV, LAMP2, Angiopoietin-like 1, ERAP2, PCDX8, ALKP, TMEFF2, IFN-alpha/beta R2, STOM, HSP20, Ck beta 8-1, IL-2 R beta/CD122, NrCAM, MMRN1, OSCAR, IL-21 R, PTMA, BLMH, PLS3, IL-10, CPM, cIAP-2, Pref-1, GASP-1/WFIKKNRP, FAP, Fibrinogen, PPCS, LFA-1 alpha, Mcl-1, DcR3/TNFRSF6B, Mesothelin, TACI/TNFRSF13B, Chemerin, WISP2, GM-CSF, DLL4, TLS/FUS, AGA, BTC, Chromogranin B, HMGB3, CFVII, Cryptic, CCR6, CrkL, 14-3-3 beta, TGF-beta RI/ALK-5, EphA 1, Trypsin 1, Lipocalin-1, Podocalyxin, sgp130, Lipocalin-2, Caspase-3, ITIH4 a, FSH, Ras, PTP kappa, TIMP-1, Calsyntenin-1, MARCKS, ARP19, Fibronectin, Activin RIB/ALK-4, Chitobiase, OSBP1, IL-23, IL-12 R beta 1, GCSH, PLOD2, Nectin-3, GRP75, Soggy-1, MIP-3 alpha, GFR alpha-4, HMGB1, PCK2, LRP-1, MMP-8, HSP70, EPCR, Epiregulin, Gasl, CTLA-4/CD152, IL-27, TGF-beta 1, Attractin, BNIP2, BMP-5, PKLR, CCR3, Histone H2A, PDGF-C, IL-17B, Osteoactivin/GPNMB, CPE, CD40/TNFRSF5, CA1, Triosephosphate isomerase/TPIS, ADAMTS-17, EYA2, GFR alpha-1, Amylin, DMP-1, NUP98, SERPING1, CKB, CCR2, pro-MMP13, ApoC1, Glucose 6 Phosphate Dehydrogenase/G6PD, Caldesmon/CALD1, TLR2, NGF R, PSA-Free, COCO, MRP 1, MCAM, GRP78, IL-9, IL-1 R9, NAIP, RBP4, PABP, CEACAM-1, ADAMTS-5, ALPP, GPX1, Cathepsin X/Z/P, ApoB, Contactin-2, LRP-6, MMP-2, MFRP, Survivin, Siglec-1, PD-ECGF, cTnT, Thioredoxin-1, PGD, RPS23, TPX, LAMP, Myotrophin, SSTR5, IP-10, PGRPL, GDF7, FAM20C, ARFBP1, Activin RIIA, Sonic Hedgehog (Shh N-terminal), ApoC2, CFI, Adipsin, C7, ApoM, HRG, Fibulin 3, HINT1, GPBB, GDF5, Histone H1.3, RELM beta, glutathione S transferase Omega 1/GSTO1, Serpin A3, ErbB2, XIAP, IBSP, MICA, Desmocollin-3, Prolactin, Leptin (OB), WISP-1/CCN4, Aldolase B, NPAS3, LOX-1, hnRNP G, PACS1, BIK, Glycerol 3 Phosphate Dehydrogenase, Olfactomedin-2, GFR alpha-2, MSH6, ANGPTL4, Prouroguanylin, PHAP1, FKBP25, BMP-8, CFHR 1, Osteocalcin, HBZ, HOXD11, LEDGF, NeuroD1, RanGAP1, NF-M, SOX17, PYY, IL-20, Cytochrome c, IL-15, CA 15-3, Hemoglobin, DCBLD2, Serpin I1, DLL1, FGF-21, RNASE6, Annexin A7, PCCA, GLIPR2, Desmuslin, C9, Proteasome 20S b7, ARX, LIF R alpha, Cis, Chymase, Prion protein PrP/PRNP, IFN-gamma, CNOT1, UROD, IL-1 R6/IL-1 Rrp2, PER1, CFHR2, Thymidine Kinase-1, PTP gamma, LBP, BCAM, NM23-H1/H2, Lysozyme, Frizzled-5, PARC/CCL18, ROR1, Serpin A8, Persephin, IL-13 R alpha 1, IGFBP-3, Neurturin, perilipin 3, PSMB5, PLUNC, Cathepsin G, Siglec-9, MMP-15, Frizzled-7, ARB1, CL-P1, Glypican 3, MFG-E8, GATA-3, Frizzled-6, beta B1 Crystallin/CRYBB1, Siglec-5/CD170, TOPORS, PIN, Hemoglobin A1c, S100A8, EphB4, CLC, Cystatin A, Transthyretin, GSR, GAPDH, Trappin-2, Plastin L, PSMA1, Cathepsin S, IGFBP-5, LILRA3, GITR Ligand/TNFSF18, KRT31, KCTD10, BTD, LYVE-1, ACE, ECM-1, ZNF671, FoxP3, ROBO4, Cystatin C, BIRC6, Vitronectin, beta-Catenin, beta-I Tubulin, E-Cadherin, IL-1 sRII, Plectin, Spinesin, Endorepellin, Glut2, Insulin R, Serpin D1, Azurocidin, RPS10, Catalase, Glut5, HAI-2, FGFR1 alpha, S100A4, ARPC3, Properdin, Glyoxalase II, Netrin-4, FABP3, ZBTB4, LIMPII, Neuritin, BMP-3b/GDF-10, Vasorin, Cortactin, Cystatin D, Smad 1, MCP-4/CCL13, Syndecan-1, Osteopontin, ApoE, APN, IFN-alpha/beta R1, Fas/TNFRSF6, Erythropoietin, ApoB100, Cathepsin H, TWEAK/TNFSF12, Chordin-Like 1, Pentraxin3/TSG-14, AFP, CD61, Cathepsin D, DOTIL, Desmocollin-2, URB, PRSS3, MASP3, ADAMTS-19, Ephrin B1, TGF-beta 3, ApoH, ALDH1A1, Nectin-1, GFAP, KLK-B1, Secretogranin V/SCG5, Peroxiredoxin 3, EphB6, MYHC, NABC1, PSMD1, AgRP, IL-23 R, Galanin, PIK31P1, IL-1 F10/IL-1HY2, IL-28A, SOX4, ANK, PON1, Uromodulin, PPOX, Histone H4, Metallothionein, FOLR3, Neurokinin-A, Protein p65, IL-33, HDGF, APLP-1, Frizzled-3, PGRP-S, SOD4, SERPINB1, Tenascin C, GMF beta, Fyn, HPR, Neuropilin-2, Lamin A+C, ZC3H4-N-t, GSTP1, PON2, DCXR, GRO, Hornerin, COX-2, S100A10, 53BP1, PKM2, 5-100b, Lamin B1, PZP, Chitotriosidase, Osteocrin, PlGF, LOK, ALBUMIN, SHANK1, TLR1, HADHA, ApoD, PA2G4, KIF3B, Ubiquitin+1, TXNRD2, Eotaxin/CCL11, HCFC1, IL-20 R beta, Pancreastatin, FGF-10/KGF-2, Brevican, CES1, TIMP-2, MMP-10, CD30 Ligand/TNFSF8, GIP, Kallikrein 10, Ficolin-3, HNF-3 alpha/FoxA1, Thyroglobulin, TFPI, ICAM-3 (CD50), RPL14, S100A9, CA2, Hoxb3, Serpin A9, IL-20 R alpha, TFF1, Pro-BDNF, NCAM2, NPTXR, Guanylin, ALP, TMEFF1/Tomoregulin-1, PSA-total, KIAA1468, IL-7 R alpha, HSP10, GASP-2/WFIKKN, SLPI, Neogenin, Cerberus 1, PSMA7, Beta Defensin 4, FIH, CHC17, Semenogelin 1/SEMG1, hHR23b, Proteasome 20S alpha, Histone H3.3, SOST, EV15L, Fetuin A, Fetuin B, GULPI/CED-6, WIF-1, GDF3, INSL3, APC, TSLP, ROCK1, TRA-1-60, HOXA10, MYH7, ACLY, EVC2, CTGF/CCN2, TRA-1-81, 14-3-3 sigma, NELL2, Ferritin, Cytochrome C, B3GNT2, Fibrinopeptide A, PISD, SAMSN1, Glut3, HSP40, PD-1, PDGF R beta, SNCG, ROCK2, CRTH-2, MP1, CD200, PDIA6, Grb2, CNTF R alpha, F11, Frizzled-1, BMP-9, ROR2, L-Selectin (CD62L), Clusterin, AKR1C3, NCAM-1/CD56, S100P, COMP, FGFR1, PARK7, Laminin 2 alpha, PI 3-Kinase C2 beta, IRE1, Filamin B, NT5C3, Lumican, FGFR2, AIF, IL-34, Multimerin 2, Latent TGF beta bp2, ADM, Inhibin beta, FOLR1, SET, Progranulin, RELM alpha, Endothelin Receptor A, FABP4, PPP2R5C, ApoE3, MN1, RPS12, MLCK, INSRR, 14-3-3 epsilon, HP1BP3, Perilipin-1, Furin, ABL1, Mannosidase II, IL-17E, Grainyhead-like protein 1 homolog/GRHL1, Neurotrimin, CLIC1, LOXL1, 14-3-3 theta, RhoGDI, ACTH, Afamin, FBPase 1, Plasminogen, Kallikrein 11, Desmoglein-1, Myoglobin, Contactin-4, PECAM-1/CD31, ADH1C, ATP5O, NOV/CCN3, CRTAM, Serpin B3/SCCA1, MBL, CA 125, Smad 7, Growth Hormone (GH), OX40, Serpin A5, TRP-1, PEPSINOGEN 11, PEBP4, mTOR, hnRNP L, TACE, 14-3-3 eta, IL-17C, MMP-7, Kallikrein 7, AFG3L2, VEG1/TNFSF15, APP, LAIR1, Ran, Kallikrein 14, HSP90, Nesfatin, p27, TIM-1, Pancreatic Polypeptide, MYO5A, CPNE3, Peroxiredoxin 2, Nebulin, Aldehyde Oxidase 1/AOX1, BAZ2B, Actinin alpha 1, CA3, CCT3, MMR, Progesterone, HMGB2, PDX-1, Gastrokine 1, Factor XIII, TGF-beta 2, MMP-12, Caspase-8, PSMC3, ITM2B, PDLIM1, Plexin B1, H6PD, IL-12 p70, NAP1L1, NPM1, LRP 4, Prostasin, p21, SART1, SEZ6L2, VSIG4, SEMA3A, Hemoglobin subunit gamma 2/HBG2, IL-13, ANGPTL6, NR3C3, PEDF, Livin, AB13BP, Noelin, HTRA1, FABP5, Kremen-2, SCGF, RPS3, B4Ga1T1, ACK1, APOA1BP, ADAMTS-1, THOP1, IL-7, TSH, CLIP170-N-t, EphA3, IL-24, Ntnl, Fibrinogen gamma chain/FGG, Rab7a, SIM2, Neuropeptide B, HCR/CRAM-A/B, Serpin A12, OCT3/4, FER, ITIH3, LIN41, Mer, Hepassocin, PSMD9, hnRNP A1, BCHE, Omentin, SF20, IRS2, URB2, GPX3, MMP-16/MT3-MMP, GCLC, Cytokeratin 18, FH, IL-17RC, FGF-5, GFR alpha-3, GDI2, Lamin B2, ELAVL1, UGGT, IL-17R, CTACK/CCL27, DBI, KRTDAP, SAA, MYH2, CRTAC1, HEG1, Annexin A2, P-selectin, PAI-1, Factor XIII B, Advillin-N-t, Destrin, LUZP1, Serpin A10/ZPI, HSP32, Kallikrein 5, OIT3, Dkk-1, KRTHA3B, ENO1+ENO2+ENO3, Endocan, MSHa, AKR1B1, TXK, Pro-Cathepsin B, SOX2, JAM-A, SERTAD2, BMP-7, SPINK1, CLIC4, Human Agrin, Aldolase A, UNC5H4, GLP-1, ERRa, EphB2, C5b-9, RNA Polymerase II/POLR2A, ASPH, ANP, Antithrombin III, Cytokeratin 14, PYK2, GRP, AHNAK, hCG alpha, SorLA, EFTUD2, Endorphin Beta, Cytokeratin 17, USP5, Granzyme A, CA 9, QPRT, JARID2, S100A1, ADAMTS-L2, Pleckstrin, RELT/TNFRSF19L, IBP160, nNOS, GADD45A, C-peptide, Moesin, Hepcidin, CCR1, Pro-MMP-7, CLEC3B, Bax, HSP60, PA1VB, HAI-1, FoxO1, SOD1, APCS, Desmoglein-2, ProSAAS, ALDH9A1, EphA4, C4.4A, Corneodesmosin, MICB, HPD, CAD, HSPA8, RPS20, Serpin A7, TNK1, IDUA, SHP-1, FGF-11, Serpin A11, TWF2, SSEA-1, Proteasome subunit beta type 2/PSB2, FLG2, MIP-1d, p53, Kallikrein 6, SHBG, Hemopexin, GRP, PTN, DEFA6, Talin1, NASP, MIP 2, EIF3S2, VCP, Chem R23, Ceruloplasmin, TFF3, HN1, ITIH2, APJ, HPRT, RYK, EN2, ETL, TRKB, GM2A, KRT82, ERp29, MMP-13, ATPB, Cardiotrophin-1/CT-1, CBP, ZC3H8, Presenilin 2, CALML5, Cystatin B, AR (Amphiregulin), Presenilin 1, SART3, S100A7, Laminin gamma 1, LPS, MANF, ASH2L, GLRX1, NRG3, LH, ENSA, FRY, DDX3Y, GNB1, Proteasome 20S alpha 5, NF1, Proteasome 26S S5, TRPM7, Oxytocin-neurophysin 1/OXT, CIRL, Thymosin b10, BPIFB1, VIP Receptor 2, MFAP4, Fibrillin 1, Desmin, PAK7, CD27/TNFRSF7, Integrin alpha V, HRSP12, 14-3-3 zeta, SAA4a, Syndecan-3, Cezanne, PEPSINOGEN I, PPARg2, LTBP4, GATM-C-terminal, IL-17D, IL-12 p40, TPA, SOD-3, Serpin B6, Legumain, OBCAM, MCP-2, CA 19-9, IL-10 R beta, Procalcitonin, Thrombin, IL-1 F7/FIL1 zeta, EHD3, Gelsolin, Calbindin D, FCGBP, CHORDCI, gamma Catenin, BACE-1, Calreticulin, EphA8, Granzyme M, Thrombospondin-2, Wilms Tumor 1, FOXN3, SPEN, VDUP-1, POMC, Tyk2, C6-N-t, PDE1B, TAB182, IL-16, Rbm15, Cytokeratin 19, SOD2, Eosinophil derived neurotoxin/EDN, Pro-MMP-9, Lubricin, GMNN, 67LR, TRPS1, Dopamine beta Hydroxylase/DBH, ITGB4BP, hnRNP U, IDH1, SynCAM, KIAA1967, CEA, Resistin, Syntaxin 7, NET1, CS, COL19A1, EphB1, EPPK1, C9orf40, LOX, Lymphotoxin beta R/TNFRSF3, Neuropeptide Y, p39, DDT, MCMP2, GNPTG, Angiopoietin-like 2, CIP29, TOP2B, Corticosteroid-binding globulin, non-muscle Myosin IIA/Myosin, BAFF, C2, PIxdc2, FUCA2, Ube2L3, DMRN9, CARHSP1, GDF9, SMAC, MAGP-2, CYTL1, GARNL1, EMSY, BMPR-IB/ALK-6, PCNA, Apex1, LAMP1, Filamin A, pro-Glucagon, VEGF R1, Beta 2M, IL-10 R alpha, ROS, HE4, ZDHHC18, ALK, CLPS, RPL17, Proteasome subunit beta type 4/PSB4, Ubiquitin, LCMT2, Versican isoform V0, hnRNP A2B1, Envoplakin, GPCR GPR116, LTK, Vasopressin, Vitamin D Receptor, SDF4, TRPC1, CA150, COTL1, HMGN2, NAPRT1, hGH, SMA, Glutamyl hydrolase gamma/CGH, CCL14/HCC-1/HCC-3, GRHPR, Prosaposin, COLEC10, TROPONIN I, MDH2, PSP, Ghrelin, MTUS1, Netrin G2, ALS, Notch-2 ICD, FBP 38, FAK, Intergrin a6, DAN, BLC/BCA-1/CXCL13, Troponin C, PF4V1, G3BP, ADAMDEC1, CCDC126, ACACA, EphA5, Hck, NRG2, hnRNP C1+C2, MYL3, Peroxiredoxin 5, Vitamin K-dependent protein S, PTK 7, UQCRH, SYK, CART, Serpin A4, TXNDC4, Apo (a), APM2, ITGB5, 14-3-3 gamma, Dermcidin, AKR7A2, ORP150, VWF, Cytokeratin 4, GPI, CCDC25, MIP-1b, Midkine, DSPG3, AKAP9, BAD, Apolipoprotein L 2, LMW-PTP/ACP1, EFEMP2, HTRA2, Kallikrein 8, KLF4, EMILIN1, XEDAR, Aconitase 1, CHI3L1, hCGb, DARS2, UPB1, ERp72, HIPIR, BD-1, Ctip2, D4 GDI, CCK, PCPE-1, CRP, Cux2, MAGI2, MyBPC3, ARP2/3, EEF2, Kallikrein 2, Tryptophanyl, LTA4H, PGAM1, PSMA2, alpha 1,2 Mannosidase IA/MAN1A1, Cytokeratin 16, SRMS, ODA, C3orf75, FASTKD5, CETP, DPP3, ARFGEF3, Calpain 1, Csk, Cytokeratin 15, DEFA1/3, Nucleobindin 1/NUCB1, Factor XII, ENO1, BRSK1, fast skeletal Myosin, Factor V, ASXL1, mGLUR5, Cytokeratin 10, ESR1, beta III Tubulin/CUBB3, LDHB, TRPC6, Serotonin, p23, CPA1, Ahsp, Kilon, Protein Z, Calpastatin, BIN2, EphB3, MFI2, Cytokeratin 3, EPHX2, Cytokeratin 5, PCAF, ASK1, CLTA, CNDP1, MPCA, Mimecan, HSC70, Fumarylacetoacetate hydrolase/FAH, GHRF, ADH1B, ITIH1, DNER, MBP, Apelin, LYPA1, CACNB4, BPGM, Cadherin 22, HIBADH, VGF, ABAT, G0/G1switch 2, Ephrin B2, SCG3, ERAB, CHREBP, Hemoglobin subunit delta/HBD, C1qTNF1, Haptoglobin, D-Dimer, Calmodulin, EphA7, alphaTubulin, PRSS23, Cytokeratin 20, Tec, Coronin 3, TIM-4, CD 163, MGP, Aspartate Aminotransferase/AST, MYH6, Karyopherin beta 1, DR3/TNFRSF25, CECR1, ACTBL2, CNN2, BMPR-IA/ALK-3, BMP-4, GDI1, TYRO10, TAF4, hnRNP M1-M4, ZAP70, Stathmin 1, HLA-C, Argininosuccinate Lyase/ASL, Integrin beta 6, TRF 2, Chromogranin C, CLEC14A, ENPP2, Itk, MCM, Bcl-w, PI 3Kinase p85 beta, PTPRD, LEKTI/SPINK5, Lyn, Fen 1, Factor IX, CRMP2, EPB41, MINA, PCBP1, Lck, KHSRP, DAK, IL-1 R4/ST2, Histone H2A.Z, ESD, C04A2, ZAG, C8G, HABP2, Histone H1.2, ACAA2, Cytokeratin 13, Bassoon, Alpha 1 Microglobulin, COL9A3, BAF57, PTH, ART3, ADAMTS-4, EEF1G, Androgen Receptor, MATK, KCC3, Eps 15, Non-muscle Actin/Actin, Chromogranin A, GST, FBP2, BID, MMP-19, MDH1, Selenoprotein P, Arp2, KMT2B, CPS1, Calretinin, Apolipoprotein F, ACAA1, HSP27, CEPS7, IGFBP-1, PCMT1, BPIL1, eIF4A1-N-t, Alpha Lactalbumin, PDGF R alpha, CENPF, Creatine Kinase MM/CKMM, Asialoglycoprotein Receptor 2/ASGR2, Phosphoserine Aminotransferase/PSAT1, Gastrin, Aldolase C, CAPZA1, IDH3A, Keratin 38, GOT2, Alpha Fodrin, GLUD1, D6, GBE1, Krt73, E1 Ubiquitin Activating Enzyme/UBA1, BCOR, CPN1, PTEN, Cathelicidin, GPLD1, MCM5, NQO2, GCDFP 15, RET, A1BG, HEXA, Acetyl-CoA acetyltransferase/ACAA, Glucosidase 2 subunit beta/PRKCSH, KRT72, KIF5B, PPP2RIB, gamma-Thrombin, Alcohol Dehydrogenase/ADH, EHD1, COPS8, FRK, IGF2BP2, alpha Glucosidase II, KSR1, CPN2, LAG-3, AK2, PEPD, ADAS, Creatinine, COL4A3, LMAN2, RIP1, Cytokeratin 9, SPARCL1, Filamin C, MIP-3 beta, KRT85-N-terminal, LAD, GOLPH4, Cytochrome b5, ADH4, ARPC2, LYRIC, Angiopoietin-1, FDPS, Apolipoprotein L 1, DPEP2, Vitamin D-BP, Ankrd26, APA, ArgRS, Fibrinopeptide B, LAP3, Ihh, ALDH16A1, IQGAPI, LASP1, Integrin b1, DPPI, TRAP220, Glutathione Synthetase/GSS, BASP1, Btk, ATP5A, Keratin 36, ECHS1, Desmocollin 1, DRIL1, LTF, GART, Contactin-3, S100 A8/A9, Arp3, GOLPH2, ISOC2, alpha Actinin 4, GREMLIN, Frizzled 8, LAM b1, PTHLP, LAF4, MMP-20 and any combination thereof.

In various aspects, the exosome composition may comprise at least one ECM component wherein the at least one ECM component is present at a higher concentration than a concentration of the ECM component in a comparable exosome preparation. For example, the concentration of the ECM component may be at least 5 times, at least 10 times, at least 20 times, at least 30 times, at least 40 times, or at least 50 times the concentration of the ECM component in a comparable exosome preparation.

In one example, the concentration of the ECM component may be at least 5 times the concentration of the ECM component in a comparable exosome preparation and in further aspects, the ECM component may be selected from: Cysteine-rich Protein 1, PIM2, Cadherin-13, Beta IG-H3, EG-VEGF/PK1, Cyclophilin A, Dkk-3, BMP-3, QDPR, PAM, EDAR, EGF R/ErbB1, ALCAM, CXCR3, SBP-1, BCMA/TNFRSF17, CCL28/VIC, IL-29, HSP47, VE-Cadherin, 1-309, TGF-beta RIII, CCR8, Fractalkine, TCN1, RSU1, uPAR, VEGF-D, PRELP, TGF-beta RII, Thrombopoietin (TPO), Endothelin, S100A6, Angiogenin, TIMP-4, MSP alpha Chain, Activin A, DMGDH, Serpin B8, TRAIL R3/TNFRSF10C, CFHR5, Caspase-14, PRDX 1, FGF-12, CXCR5/BLR-1, Semaphorin 7A, SPINK7, NT-4, TNF RII/TNFRSF1B, 6Ckine, SerRS, Angiostatin, Angiopoietin-like Factor, B7-1/CD80, Protein C, Tcf20, TROY/TNFRSF19, EMAP-II, CSH1, TLR4, RPLP0, ErbB3, RPL11, PGK-1, FGF-16, Plakophilin 1, PRCP, RAGE, Insulin, TSR2, NT-3, USP14, VDAC1/Porin, Proteasome 20S a+b, M-CSF, IL-2, ICAM-1, NEDD8, PRG2, Insulysin/IDE, ICAM-2, MMP-1, Salivary alpha amylase/aAmylase, IL-17F, Galectin-1, Lymphotoxin beta/TNFSF3, TBCA, PREP, VAP-A, Utrophin, YB1, VAP-1, CFHR4, FGF-20, Cyclophilin B, RNASE4, SBSN, FGF R4, FGF-17, PGLS-C-t, Eotaxin-3/CCL26, RREB1, TMEM223, ADAMTS-15, Semenogelin II/SEMG2, C3a, RPL12, GDF8, IGF-II, RPS25, Follistatin-like 1, Smad 5, Notch-2, I-TAC/CXCL11, TRANCE, MMP-3, uPA, WDR1, UQCRB, DR6/TNFRSF21, BMP-15, PSMA4, ErbB4, Gephyrin, beta-NGF, BMP-2, BMP-6, NAP-2, LECT2, FGF-13 1B, Reg3A, CD14, SHIP, RPL5, VEGF, IL-1 F5/FIL1delta, RPS28, TUBA6, Endostatin, MMP-9, CK-MB, CapG, IL-11, Ribonuclease A, Eotaxin-2/MPIF-2, GLO-1, TLR3, HGF, Sterol carrier protein 2/SCP2, Visfatin, SHC1, IL-18 R beta/AcPL, SIGLEC14, PRTN3, Contactin-1, CV-2/Crossveinless-2, EDG-1, CXCL14/BRAK, TIMP-3, Serpin A1, Annexin A1, TGM3, CXCR6, PGM1, Osteoprotegerin/TNFRSF11B, Coagulation Factor III/Tissue Factor, M-CSF R, MDC, FAM3B, MMP-11/Stromelysin-3, SCF R/CD117, TGF-beta 5, Titin, sFRP-3, IL-1 beta, HCC-4/CCL16, TRAIL/TNFSF10, Fascin, BNP, ADAMTS-13, PLOD1, FLRG, LDHA, LIF, YY1, NME3, ESAM, RPS19, EpCAM, TAGLN2, CXCL16, BTF3, Hemoglobin subunit beta/HBB, TRADD, Metavinculin, BDNF, Galectin-7, PPP2R4, FACX, PDZD2, IL-26, FGF-9, Fibrinogen-like 2, Plexin B2, Thrombomodulin, Dtk, TRAIL R2/DR5/TNFRSF10B, PNP, ANGPTL8, B7-H3, ACLP, Galectin-3, p73, IL-4, IL-13 R alpha 2, TOB2, Claudin-3, IL-8, VEGF-C, IGF-1 SR, Tenascin X(1), Lefty-A, Thrombospondin-1, OSM R beta, SUCLG1, PDGF-AB, IL-6 R, IL-18 BPa, PGAM2, Cripto-1, FGF-23, GSTM1, ICAM-5, RPL10, Ribonuclease Inhibitor, ARTS1, Periostin, UCH-L1, Zyxin, RPL10A, PDLIM5, IL-15 R alpha, FAM3C, Tropomyosin 3, LZTS1, LIGHT/TNFSFI4, Osteoadherin(2), SHMT1, CCR9, TWEAK R/TNFRSF12, TPP1, ADAMTS-10, RCL, PCDH7, MIG, SPARC, SH3BGRL, Thrombospondin-4, UFM 1, Prostaglandin D Synthase/PTGDS, GPR-39, SPTBN1, BLVRB, RKIP, 4-1BB, Decorin, CRIM 1, PCSK9, STI1, IL-22 BP, VEGF R2 (KDR), Ficolin-2, CXCR4 (fusin), SIGIRR, IFN-beta, Cyclin D1, MIP-1a, RPS11, Alpha 1 AG, BLAME, Cystatin E/M, GM-CSF R alpha, Uteroglobin(1), Trypsinogeb-2, MCP-3, Erythropoietin R, Proteasome subunit alpha type 6/PSMA6, TGF-alpha, Flt-3 Ligand, Nanog, TNF-alpha, Spectrin beta-5, VNN1, BMP-1, FGF-7/KGF, OSM, FGF R5, Transferrin, C5/C5a, ApoA1, TCP1 eta, Galectin-3BP, PTPRZ, TRAIL R1/DR4/TNFRSF10A, Six3, SORD, CNTF, GDNF, BMPR-II, CXCR2/IL-8 RB, FGF-8, RPS5, CRF21, PGDF/PHGDH, FABP1, SLURP1, CEACAM-8/CD66b, UNC45A, Adiponectin/Acrp30, MMP-25/MT6-MMP, SMC4, Ornithine Carbamoyltransferase/OTC, IFN-gamma R1, CCR4, Proteasome beta 1, Talin1&2, Prohibitin, MMP-24/MT5-MMP, SP-D, Nidogen-2, PTPRS, SIRP beta 1/CD172b, APRIL, ACE-2, IL-6, HGFA, E-Selectin, GATA-4, VEGF R3, UBE2D3, BAFF R/TNFRSF13C, Layilin, Cytokeratin 8, Profilin 1, Cathepsin B, Marapsin, Lymphotactin/XCL1, Nidgen-1, MEP1A, MIF, IL-1 F8/FIL1 eta, MMP-14, HB-EGF, Latent TGF-beta bp1, C8B, SMPD4, ADAMTS-18, FGF Basic, IL-12 R beta 2, MINPP1, URP2, Glycoprotein V, LRG1, ACPP, AlphaA Crystallin/CRYAA, EDA-A2, SH3BGRL3, Serpin F2, CD40 Ligand/TNFSF5/CD154, CPEB3, A2M, Activin B, SREC-II, EGF, FGF-19, Myoferlin, Endoglin/CD105, RECK, ADAM-9, SSEA-4, DDAH1, P-Cadherin, IL-22 R, Glut1, Symplekin, S100A11, SLITRK1, GCP-2/CXCL6, SDPR, IGF-II R, P4HB, TNF-beta, IL-1 R8, IL-1 alpha, Angiopoietin-4, TCCR/WSX-1, GITR/TNFRF18, ILK, TCEB2, RPL22, DEP-1, FGF-18, TL1A/TNFSF15, EphA6, IL-36RN, Tarc, UROC1, Activin C, FASN, PYGL, Somatostatin, Musk, PLA2GIB, IL-1 R3/IL-1 R AcP, FGF-6, IL-18 R alpha/IL-1 R5, Tie-2, NIT2, PF4/CXCL4, TPM1, GDF11, IGFBP-6, Thymopoietin, FUCA1, CRHBP, C1qR1, STAT3, TPM4, Follistatin, Laminin b2, IL-1 sRI, CCR7, ApoA2, ENA-78, Myosin 18B, Desmoplakin, Neurabin 1, FGF-4, PDGF-BB, PCBP2, P20Sb3, IGF2BP1, Chordin-Like 2, UNC-13 Homolog D, Enolase 2, Angiopoietin-2, TFF2(1), RHOC, SUMO3, DGK, HVEM/TNFRSF14, GRO-a, GALNT2, TECK/CCL25, Notch-1, Cystatin S, IL-2 R alpha, WNK2, eIF5A, TrypsinPan, SCF, CD30/TNFRSF8, IL-1 F6/FIL1 epsilon, CutA, CFL1, TRAIL R4/TNFRSF10D, MBD2, UBE2N/Ubc13, PI 16, DANCE, FABP2, IGFBP-4, NEP, NRG1 Isoform GGF2, IL-2 R gamma, MAC-1, MPO, SerpinE2, GDF1, IL-17, Orexin A, Kremen-1, Smad 4, IL-17B R, GCSF, Annexin V, IL-31, TRAP1, Transketolase/TALDO, pIgR, Brg1, BMX, MAN1, Orosomucoid 2, RAP1AB, VEGF-B, SLC38A10, RPS2, RANTES, SerpinB4, Nestin, Complement factor H, MAPRE1, PDGF-AA, Reg1A, MUCDHL, SSTR2, IGSF4B, TSG-6, Orexin B, Quiescin Q6, IGFBP-2, IGFBP-rp1/IGFBP-7, Dystroglycan, Alanine Transaminase/ALT, FKBP12, Growth Hormone R (GHR), MCP-1, IL-21, RANK/TNFRSF11A, HRG-beta 1, ACTC1, Ribonuclease T2, B3GNT1, Src(1), PCYOX1, Leptin R, IL-19, CXCR1/IL-8 RA, PTP mu, IL-1 ra, PDGF-D, HEXB, ERp57, PLC-gamma 1, Nesprin2, Frizzled-4, B7-H2, NAGLU, Serpin B5, TNF RI/TNFRSF1A, IL-1 F9/IL-1 H1, Histone H2B K, OX40 Ligand/TNFSF4, Aminoacylase, Transaldolase 1/TALDO1, Glucagon, IFRD1, sFRP-4, IL-22, Kininostatin/kininogen, PRDM13, CCR5, C 1q, AMPKa1, EXTL2, POR, Smad 8, TXNDC5, IL-17RD, TREM-1, SDNSF, FKBP51, Complement Factor B, Cadherin-6, VCAM-1 (CD106), 11b-HSD1, Tie-1, Vimentin B, DISC 1, RPL7A, GDF-15, IL-31 RA, IL-5 R alpha, p16 ARC, EN-RAGE, Biglycan, DSCAM, Aggrecan, DCI, Cathepsin A, HGFR, sFRP-1, IL-4 R, IL-5, FGF R3, Activin RIA/ALK-2, Prdx6, Cathepsin L, Ezrin, TAXIBP3, FGF-BP, AMICA, KMD4B, Artemin, Axl, Claudin-4, SDF-1/CXCL12, FADD, MAP1A, ABCF1, Annexin A6, G-CSF R/CD 114, TSLP R, BRCA 2, EphA2, Cystatin SN, Fas Ligand, Pappalysin-1, ME1, 2B4, Fc RIIB/C, Dkk-4, alpha-Synuclein, Neural Cadherin, ANGPTL3, C 1q S, ATBF1/ZFHX3, IGF-1, IL-3, IL-3 R alpha, Semaphorin 6B, DPPIV, LAMP2, Angiopoietin-like 1, ERAP2, PCDX8, ALKP, TMEFF2, IFN-alpha/beta R2, STOM, HSP20, Ck beta 8-1, IL-2 R beta/CD122, NrCAM, MMRN1, OSCAR, IL-21 R, PTMA, BLMH, PLS3, IL-10, CPM, cIAP-2, Pref-1, GASP-1/WFIKKNRP, FAP, Fibrinogen, PPCS, LFA-1 alpha, Mcl-1, DcR3/TNFRSF6B, Mesothelin, TACI/TNFRSF13B, Chemerin, WISP2, GM-CSF, DLL4, TLS/FUS, AGA, BTC, Chromogranin B, HMGB3, CFVII, Cryptic, CCR6, CrkL, 14-3-3 beta, TGF-beta RI/ALK-5, EphA1, Trypsin 1, Lipocalin-1, Podocalyxin, sgp130, Lipocalin-2, Caspase-3, ITIH4 a, FSH, Ras, PTP kappa, TIMP-1, Calsyntenin-1, MARCKS, ARP19, Fibronectin, Activin RIB/ALK-4, Chitobiase, OSBP1, IL-23, IL-12 R beta 1, GCSH, PLOD2, Nectin-3, GRP75, Soggy-1, MIP-3 alpha, GFR alpha-4, HMGB1, PCK2, LRP-1, MMP-8, HSP70, EPCR, Epiregulin, Gasl, CTLA-4/CD152, IL-27, TGF-beta 1, Attractin, BNIP2, BMP-5, PKLR, CCR3, Histone H2A, PDGF-C, IL-17B, Osteoactivin/GPNMB, CPE, CD40/TNFRSF5, CA1, Triosephosphate isomerase/TPIS, ADAMTS-17, EYA2, GFR alpha-1, Amylin, DMP-1, NUP98, SERPING1, CKB, CCR2, pro-MMP13, ApoC1, Glucose 6 Phosphate Dehydrogenase/G6PD, Caldesmon/CALD1, TLR2, NGF R, PSA-Free, COCO, MRP 1, MCAM, GRP78, IL-9, IL-1 R9, NAIP, RBP4, PABP, CEACAM-1, ADAMTS-5, ALPP, GPX1, Cathepsin X/Z/P, ApoB, Contactin-2, LRP-6, MMP-2, MFRP, Survivin, Siglec-1, PD-ECGF, cTnT, Thioredoxin-1, PGD, RPS23, TPX, LAMP, Myotrophin, SSTR5, IP-10, PGRPL, GDF7, FAM20C, ARFBP1, Activin RIIA, Sonic Hedgehog (Shh N-terminal), ApoC2, CFI, Adipsin, C7, ApoM, HRG, Fibulin 3, HINT1, GPBB, GDF5, Histone H1.3, RELM beta, glutathione S transferase Omega 1/GSTO1, Serpin A3, ErbB2, XIAP, IBSP, MICA, Desmocollin-3, Prolactin, Leptin (OB), WISP-1/CCN4, Aldolase B, NPAS3, LOX-1, hnRNP G, PACS1, BIK, Glycerol 3 Phosphate Dehydrogenase, Olfactomedin-2, GFR alpha-2, MSH6, ANGPTL4, Prouroguanylin, PHAP1, FKBP25, BMP-8, CFHR 1, Osteocalcin, HBZ, HOXDI 1, LEDGF, NeuroD1, RanGAP1, NF-M, SOX17, PYY, IL-20, Cytochrome c, IL-15, CA 15-3, Hemoglobin, DCBLD2, Serpin I1, DLL1, FGF-21, RNASE6, Annexin A7, PCCA, GLIPR2, Desmuslin, C9, Proteasome 20S b7, ARX, LIF R alpha, Cls, Chymase, Prion protein PrP/PRNP, IFN-gamma, CNOT1, UROD, IL-1 R6/IL-1 Rrp2, PER1, CFHR2, Thymidine Kinase-1, PTP gamma, LBP, BCAM, NM23-H1/H2, Lysozyme, Frizzled-5, PARC/CCL18, ROR1, Serpin A8, Persephin, IL-13 R alpha 1, IGFBP-3, Neurturin, perilipin 3, PSMB5, PLUNC, Cathepsin G, Siglec-9, MMP-15, Frizzled-7, ARB1, CL-P1, Glypican 3, MFG-E8, GATA-3, Frizzled-6, beta B1 Crystallin/CRYBB1, Siglec-5/CD170, TOPORS, PIN, Hemoglobin A1c, S100A8, EphB4, CLC, Cystatin A, Transthyretin, GSR, GAPDH, Trappin-2, Plastin L, PSMA1, Cathepsin S, IGFBP-5, LILRA3, GITR Ligand/TNFSFI8, KRT31, KCTD10, BTD, LYVE-1, ACE, ECM-1, ZNF671, FoxP3, ROBO4, Cystatin C, BIRC6, Vitronectin, beta-Catenin, beta-I Tubulin, E-Cadherin, IL-1 sRII, Plectin, Spinesin, Endorepellin, Glut2, Insulin R, Serpin D1, Azurocidin, RPS10, Catalase, Glut5, HAI-2, FGFR1 alpha, S100A4, ARPC3, Properdin, Glyoxalase II, Netrin-4, FABP3, ZBTB4, LIMPII, Neuritin, BMP-3b/GDF-10, Vasorin, Cortactin, Cystatin D, Smad 1, MCP-4/CCL13, Syndecan-1, Osteopontin, ApoE, APN, IFN-alpha/beta R1, Fas/TNFRSF6, Erythropoietin, ApoB100, Cathepsin H, TWEAK/TNFSF12, Chordin-Like 1, Pentraxin3/TSG-14, AFP, CD61, Cathepsin D, DOTiL, Desmocollin-2, URB, PRSS3, MASP3, ADAMTS-19, Ephrin B1, TGF-beta 3, ApoH, ALDH1A1, Nectin-1, GFAP, KLK-B1, Secretogranin V/SCG5, Peroxiredoxin 3, EphB6, MYHC, NABC1, PSMD1, AgRP, IL-23 R, Galanin, PIK31P1, IL-1 F10/IL-1HY2, IL-28A, SOX4, ANK, PON1, Uromodulin, PPOX, Histone H4, Metallothionein, FOLR3, Neurokinin-A, Protein p65, IL-33, HDGF, APLP-1, Frizzled-3, PGRP-S, SOD4, SERPINB1, Tenascin C, GMF beta, Fyn, HPR, Neuropilin-2, Lamin A+C, ZC3H4-N-t, GSTP1, PON2, DCXR, GRO, Hornerin, COX-2, S100A10, 53BP1, PKM2, 5-100b, Lamin B1, PZP, Chitotriosidase, Osteocrin, PlGF, LOK, ALBUMIN, SHANK1, TLR1, HADHA, ApoD, PA2G4, KIF3B, Ubiquitin+1, TXNRD2, Eotaxin/CCL11, HCFC1, IL-20 R beta, Pancreastatin, FGF-10/KGF-2, Brevican, CES1, TIMP-2, MMP-10, CD30 Ligand/TNFSF8, GIP, Kallikrein 10, Ficolin-3, HNF-3 alpha/FoxA1, Thyroglobulin, TFPI, ICAM-3 (CD50), RPL14, S100A9, CA2, Hoxb3, Serpin A9, IL-20 R alpha, TFF1, Pro-BDNF, NCAM2, NPTXR, Guanylin, ALP, TMEFF1/Tomoregulin-1, PSA-total, KIAA1468, IL-7 R alpha, HSP10, GASP-2/WFIKKN, SLPI, Neogenin, Cerberus 1, PSMA7, Beta Defensin 4, FIH, CHC17, Semenogelin I/SEMG1, hHR23b, Proteasome 20S alpha, Histone H3.3, SOST, EV15L, Fetuin A, Fetuin B, GULP/CED-6, WIF-1, GDF3, INSL3, APC, TSLP, ROCK1, TRA-1-60, HOXA10, MYH7, ACLY, EVC2, CTGF/CCN2, TRA-1-81, 14-3-3 sigma, NELL2, Ferritin, Cytochrome C, B3GNT2, Fibrinopeptide A, PISD, SAMSN1, Glut3, HSP40, PD-1, PDGF R beta, SNCG, ROCK2, CRTH-2, MP1, CD200, PDIA6, Grb2, CNTF R alpha, F11, Frizzled-1, BMP-9, ROR2, L-Selectin (CD62L), Clusterin, AKRIC3, NCAM-1/CD56, S100P, COMP, FGFR1, PARK7, Laminin 2 alpha, PI 3-Kinase C2 beta, IRE1, Filamin B, NTSC3, Lumican, FGFR2, AIF, IL-34, Multimerin 2, Latent TGF beta bp2, ADM, Inhibin beta, FOLR1, SET, Progranulin, RELM alpha, Endothelin Receptor A, FABP4, PPP2R5C, ApoE3, MN1, RPS12, MLCK, INSRR, 14-3-3 epsilon, HP1BP3, Perilipin-1, Furin, ABL1, Mannosidase II, IL-17E, Grainyhead-like protein 1 homolog/GRHL1, Neurotrimin, CLIC1, LOXL1, 14-3-3 theta, RhoGDI, ACTH, Afamin, FBPase 1, Plasminogen, Kallikrein 11, Desmoglein-1, Myoglobin, Contactin-4, PECAM-1/CD31, ADHIC, ATP50, NOV/CCN3, CRTAM, Serpin B3/SCCA1, MBL, CA 125, Smad 7, Growth Hormone (GH), OX40, Serpin A5, TRP-1, PEPSINOGEN II, PEBP4, mTOR, hnRNP L, TACE, 14-3-3 eta, IL-17C, MMP-7, Kallikrein 7, AFG3L2, VEG1/TNFSF15, APP, LAIR1, Ran, Kallikrein 14, HSP90, Nesfatin, p27, TIM-1, Pancreatic Polypeptide, MYOSA, CPNE3, Peroxiredoxin 2, Nebulin, Aldehyde Oxidase 1/AOX1, BAZ2B, Actinin alpha 1, CA3, CCT3, MMR, Progesterone, HMGB2, PDX-1, Gastrokine 1, Factor XIII, TGF-beta 2, MMP-12, Caspase-8, PSMC3, ITM2B, PDLIM1, Plexin B1, H6PD, IL-12 p70, NAP1L1, NPM1, LRP 4, Prostasin, p21, SART1, SEZ6L2, VSIG4, SEMA3A, Hemoglobin subunit gamma2/HBG2, IL-13, ANGPTL6, NR3C3, PEDF, Livin, ABI3BP, Noelin, HTRA1, FABP5, Kremen-2, SCGF, RPS3, B4GaIT1, ACK1, APOA1BP, ADAMTS-1, THOP1, IL-7, TSH, CLIP170-N-t, EphA3, IL-24, Ntnl, Fibrinogen gamma chain/FGG, Rab7a, SIM2, Neuropeptide B, HCR/CRAM-A/B, Serpin A12, OCT3/4, FER, ITIH3, LIN41, Mer, Hepassocin, PSMD9, hnRNP A1, BCHE, Omentin, SF20, IRS2, URB2, GPX3, MMP-16/MT3-MMP, GCLC, Cytokeratin 18, FH, IL-17RC, FGF-5, GFR alpha-3, GDI2, Lamin B2, ELAVL1, UGGT, IL-17R, CTACK/CCL27, DBI, KRTDAP, SAA, MYH2, CRTAC1, HEG1, Annexin A2, P-selectin, PAI-1, Factor XIII B, Advillin-N-t, Destrin, LUZP1, Serpin A10/ZPI, HSP32, Kallikrein 5, OIT3, Dkk-1, KRTHA3B, ENO1+ENO2+ENO3, Endocan, MSHa, AKRIB1, TXK, Pro-Cathepsin B, SOX2, JAM-A, SERTAD2, BMP-7, SPINK1, CLIC4, Human Agrin, Aldolase A, UNC5H4, GLP-1, ERRa, EphB2, C5b-9, RNA Polymerase II/POLR2A, ASPH, ANP, Antithrombin III, Cytokeratin 14, PYK2, GRP, AHNAK, hCG alpha, SorLA, EFTUD2, Endorphin Beta, Cytokeratin 17, USP5, Granzyme A, CA 9, QPRT, JARID2, S100A1, ADAMTS-L2, Pleckstrin, RELT/TNFRSF19L, IBP160, nNOS, GADD45A, C-peptide, Moesin, Hepcidin, CCR1, Pro-MMP-7, CLEC3B, Bax, HSP60, PARVB, HAI-1, FoxO1, SOD1, APCS, Desmoglein-2, ProSAAS, ALDH9A1, EphA4, C4.4A, Corneodesmosin, MICB, HPD, CAD, HSPA8, RPS20, Serpin A7, TNK1, IDUA, SHP-1, FGF-11, Serpin A11, TWF2, SSEA-1, Proteasome subunit beta type 2/PSB2, FLG2, MIP-1d, p53, Kallikrein 6, SHBG, Hemopexin, GRP, PTN, DEFA6, Talin1, NASP, MIP 2, EIF3S2, VCP, Chem R23, Ceruloplasmin, TFF3, HN1, ITIH2, APJ, HPRT, RYK, EN2, ETL, TRKB, GM2A, KRT82, ERp29, MMP-13, ATPB, Cardiotrophin-1/CT-1, CBP, ZC3H8, Presenilin 2, CALML5, Cystatin B, AR (Amphiregulin), Presenilin 1, SART3, S100A7, Laminin gamma 1, LPS, MANF, ASH2L, GLRX1, NRG3, LH, ENSA, FRY, DDX3Y, GNB1, Proteasome 20S alpha 5, NF1, Proteasome 26S S5, TRPM7, Oxytocin-neurophysin 1/OXT, ClRL, Thymosin b10, BPIFB1, VIP Receptor 2, MFAP4, Fibrillin 1, Desmin, PAK7, CD27/TNFRSF7, Integrin alpha V, HRSP12, 14-3-3 zeta, SAA4a, Syndecan-3, Cezanne, PEPSINOGEN I, PPARg2, LTBP4, GATM-C-terminal, IL-17D, IL-12 p40, TPA, SOD-3, Serpin B6, Legumain, OBCAM, MCP-2, CA 19-9, IL-10 R beta, Procalcitonin, Thrombin, IL-1 F7/FIL1 zeta, EHD3, Gelsolin, Calbindin D, FCGBP, CHORDCI, gamma Catenin, BACE-1, Calreticulin, EphA8, Granzyme M, Thrombospondin-2, Wilms Tumor 1, FOXN3, SPEN, VDUP-1, POMC, Tyk2, C6-N-t, PDEIB, TAB182, IL-16, Rbm15, Cytokeratin 19, SOD2, Eosinophil derived neurotoxin/EDN, Pro-MMP-9, Lubricin, GMNN, 67LR, TRPS1, Dopamine beta Hydroxylase/DBH, ITGB4BP, hnRNP U, IDH1, SynCAM, K1AA1967, CEA, Resistin, Syntaxin 7, NET1, CS, COL19A1, EphB1, EPPK1, C9orf40, LOX, Lymphotoxin beta R/TNFRSF3, Neuropeptide Y, p39, DDT, MCMP2, GNPTG, Angiopoietin-like 2, CIP29, TOP2B, Corticosteroid-binding globulin, non-muscle Myosin IIA/Myosin, BAFF, C2, Plxdc2, FUCA2, Ube2L3, DMRN9, CARHSP1, GDF9, SMAC, MAGP-2, CYTL1, GARNL1, EMSY, BMPR-IB/ALK-6, PCNA, Apex1, LAMP1, Filamin A, pro-Glucagon, VEGF R1, Beta 2M, IL-10 R alpha, ROS, HE4, ZDHHCI8, ALK, CLPS, RPL17, Proteasome subunit beta type 4/PSB4, Ubiquitin, LCMT2, Versican isoform V0, hnRNP A2B1, Envoplakin, GPCR GPRI16, LTK, Vasopressin, Vitamin D Receptor, SDF4, TRPC1, CA150, COTL1, HMGN2, NAPRT1, hGH, SMA, Glutamyl hydrolase gamma/CGH, CCL14/HCC-1/HCC-3, GRHPR, Prosaposin, COLEC10, TROPONIN I, MDH2, PSP, Ghrelin, MTUS1, Netrin G2, ALS, Notch-2 ICD, FBP 38, FAK, Intergrin a6, DAN, BLC/BCA-1/CXCL13, Troponin C, PF4V1, G3BP, ADAMDEC1, CCDC126, ACACA, EphA5, Hck, NRG2, hnRNP C1+C2, MYL3, Peroxiredoxin 5, Vitamin K-dependent protein S, PTK 7, UQCRH, SYK, CART, Serpin A4, TXNDC4, Apo (a), APM2, ITGB5, 14-3-3 gamma, Dermcidin, AKR7A2, ORP150, VWF, Cytokeratin 4, GPI, CCDC25, MIP-1b, Midkine, DSPG3, AKAP9, BAD, Apolipoprotein L 2, LMW-PTP/ACP1, EFEMP2, HTRA2, Kallikrein 8, KLF4, EMILIN1, XEDAR, Aconitase 1, CHI3L1, hCGb, DARS2, UPB1, ERp72, HIPIR, BD-1, Ctip2, D4 GDI, CCK, PCPE-1, CRP, Cux2, MAG12, MyBPC3, ARP2/3, EEF2, Kallikrein 2, Tryptophanyl, LTA4H, PGAM1, PSMA2, alpha 1,2 Mannosidase IA/MAN1A1, Cytokeratin 16, SRMS, GDA, C3orf75, FASTKD5, CETP, DPP3, ARFGEF3, Calpain 1, Csk, Cytokeratin 15, DEFA1/3, Nucleobindin 1/NUCB1, Factor XII, ENOb, BRSK1, fast skeletal Myosin, Factor V, ASXL1, mGLUR5, Cytokeratin 10, ESR1, beta III Tubulin/CUBB3, LDHB, TRPC6, Serotonin, p23, CPA1, Ahsp, Kilon, Protein Z, Calpastatin, BIN2, EphB3, MFI2, Cytokeratin 3, EPHX2, Cytokeratin 5, PCAF, ASK1, CLTA, CNDP1, MPCA, Mimecan, HSC70, Fumarylacetoacetate hydrolase/FAH, GHRF, ADH1B, ITIH1, DNER, MBP, Apelin, LYPA1, and CACNB4.

In various aspects, the concentration of the ECM component in the exosome composition may be at least 10 times the concentration of the ECM component in a comparable exosome preparation. For example, the concentration of the ECM component may be at least 10 times the concentration of the ECM component in a comparable exosome preparation and be selected from Cysteine-rich Protein 1, PIM2, Cadherin-13, Beta 1G-H3, EG-VEGF/PK1, Cyclophilin A, Dkk-3, BMP-3, QDPR, PAM, EDAR, EGF R/ErbB1, ALCAM, CXCR3, SBP-1, BCMA/TNFRSF17, CCL28/VIC, IL-29, HSP47, VE-Cadherin, 1-309, TGF-beta RIII, CCR8, Fractalkine, TCN1, RSU1, uPAR, VEGF-D, PRELP, TGF-beta RII, Thrombopoietin (TPO), Endothelin, S100A6, Angiogenin, TIMP-4, MSP alpha Chain, Activin A, DMGDH, Serpin B8, TRAIL R3/TNFRSF10C, CFHR5, Caspase-14, PRDX 1, FGF-12, CXCR5/BLR-1, Semaphorin 7A, SPINK7, NT-4, TNF RIb/TNFRSF1B, 6Ckine, SerRS, Angiostatin, Angiopoietin-like Factor, B7-1/CD80, Protein C, Tcf20, TROY/TNFRSF19, EMAP-II, CSH1, TLR4, RPLP0, ErbB3, RPL 11, PGK-1, FGF-16, Plakophilin 1, PRCP, RAGE, Insulin, TSR2, NT-3, USP14, VDAC1/Porin, Proteasome 20S a+b, M-CSF, IL-2, ICAM-1, NEDD8, PRG2, Insulysin/IDE, ICAM-2, MMP-1, Salivary alpha amylase/aAmylase, IL-17F, Galectin-1, Lymphotoxin beta/TNFSF3, TBCA, PREP, VAP-A, Utrophin, YB1, VAP-1, CFHR4, FGF-20, Cyclophilin B, RNASE4, SBSN, FGF R4, FGF-17, PGLS-C-t, Eotaxin-3/CCL26, RREB1, TMEM223, ADAMTS-15, Semenogelin II/SEMG2, C3a, RPL12, GDF8, IGF-II, RPS25, Follistatin-like 1, Smad 5, Notch-2, I-TAC/CXCL11, TRANCE, MMP-3, uPA, WDR1, UQCRB, DR6/TNFRSF21, BMP-15, PSMA4, ErbB4, Gephyrin, beta-NGF, BMP-2, BMP-6, NAP-2, LECT2, FGF-13 1B, Reg3A, CD14, SHIP, RPL5, VEGF, IL-1 F5/FIL1delta, RPS28, TUBA6, Endostatin, MMP-9, CK-MB, CapG, IL-11, Ribonuclease A, Eotaxin-2/MPIF-2, GLO-1, TLR3, HGF, Sterol carrier protein 2/SCP2, Visfatin, SHC1, IL-18 R beta/AcPL, SIGLEC14, PRTN3, Contactin-1, CV-2/Crossveinless-2, EDG-1, CXCL14/BRAK, TIMP-3, Serpin A1, Annexin A1, TGM3, CXCR6, PGM1, Osteoprotegerin/TNFRSF11B, Coagulation Factor III/Tissue Factor, M-CSF R, MDC, FAM3B, MMP-11/Stromelysin-3, SCF R/CD117, TGF-beta 5, Titin, sFRP-3, IL-1 beta, HCC-4/CCL16, TRAIL/TNFSF10, Fascin, BNP, ADAMTS-13, PLOD1, FLRG, LDHA, LIF, YY1, NME3, ESAM, RPS19, EpCAM, TAGLN2, CXCL16, BTF3, Hemoglobin subunit beta/HBB, TRADD, Metavinculin, BDNF, Galectin-7, PPP2R4, FACX, PDZD2, IL-26, FGF-9, Fibrinogen-like 2, Plexin B2, Thrombomodulin, Dtk, TRAIL R2/DR5/TNFRSF10B, PNP, ANGPTL8, B7-H3, ACLP, Galectin-3, p73, IL-4, IL-13 R alpha 2, TOB2, Claudin-3, IL-8, VEGF-C, IGF-I SR, Tenascin X(1), Lefty-A, Thrombospondin-1, OSM R beta, SUCLG1, PDGF-AB, IL-6 R, IL-18 BPa, PGAM2, Cripto-1, FGF-23, GSTM1, ICAM-5, RPL10, Ribonuclease Inhibitor, ARTS1, Periostin, UCH-L1, Zyxin, RPL10A, PDL1M5, IL-15 R alpha, FAM3C, Tropomyosin 3, LZTS1, LIGHT/TNFSF14, Osteoadherin(2), SHMT1, CCR9, TWEAK R/TNFRSF12, TPP1, ADAMTS-10, RCL, PCDH7, MIG, SPARC, SH3BGRL, Thrombospondin-4, UFM 1, Prostaglandin D Synthase/PTGDS, GPR-39, SPTBN1, BLVRB, RKIP, 4-1BB, Decorin, CRIM 1, PCSK9, STI1, IL-22 BP, VEGF R2 (KDR), Ficolin-2, CXCR4 (fusin), SIGIRR, IFN-beta, Cyclin D1, MIP-1a, RPS11, Alpha 1 AG, BLAME, Cystatin E/M, GM-CSF R alpha, Uteroglobin(1), Trypsinogeb-2, MCP-3, Erythropoietin R, Proteasome subunit alpha type 6/PSMA6, TGF-alpha, Flt-3 Ligand, Nanog, TNF-alpha, Spectrin beta-5, VNN1, BMP-1, FGF-7/KGF, OSM, FGF R5, Transferrin, C5/C5a, ApoA1, TCP1 eta, Galectin-3BP, PTPRZ, TRAIL R1/DR4/TNFRSF10A, Six3, SORD, CNTF, GDNF, BMPR-II, CXCR2/IL-8 RB, FGF-8, RPS5, CRF21, PGDF/PHGDH, FABP1, SLURP1, CEACAM-8/CD66b, UNC45A, Adiponectin/Acrp30, MMP-25/MT6-MMP, SMC4, Ornithine Carbamoyltransferase/OTC, IFN-gamma R1, CCR4, Proteasome beta 1, Talin1&2, Prohibitin, MMP-24/MT5-MMP, SP-D, Nidogen-2, PTPRS, SIRP beta 1/CD172b, APRIL, ACE-2, IL-6, HGFA, E-Selectin, GATA-4, VEGF R3, UBE2D3, BAFF R/TNFRSF13C, Layilin, Cytokeratin 8, Profilin 1, Cathepsin B, Marapsin, Lymphotactin/XCL1, Nidgen-1, MEPlA, MIF, IL-1 F8/FIL1 eta, MMP-14, HB-EGF, Latent TGF-beta bp1, C8B, SMPD4, ADAMTS-18, FGF Basic, IL-12 R beta 2, MINPP1, URP2, Glycoprotein V, LRG1, ACPP, AlphaA Crystallin/CRYAA, EDA-A2, SH3BGRL3, Serpin F2, CD40 Ligand/TNFSF5/CD154, CPEB3, A2M, Activin B, SREC-II, EGF, FGF-19, Myoferlin, Endoglin/CD105, RECK, ADAM-9, SSEA-4, DDAH1, P-Cadherin, IL-22 R, Glut1, Symplekin, S100A11, SLITRK1, GCP-2/CXCL6, SDPR, IGF-II R, P4HB, TNF-beta, IL-1 R8, IL-1 alpha, Angiopoietin-4, TCCR/WSX-1, GITR/TNFRF18, ILK, TCEB2, RPL22, DEP-1, FGF-18, TL1A/TNFSF15, EphA6, IL-36RN, Tarc, UROC1, Activin C, FASN, PYGL, Somatostatin, Musk, PLA2GIB, IL-1 R3/IL-1 R AcP, FGF-6, IL-18 R alpha/IL-1 R5, Tie-2, NIT2, PF4/CXCL4, TPM1, GDF11, IGFBP-6, Thymopoietin, FUCA1, CRHBP, CIqR1, STAT3, TPM4, Follistatin, Laminin b2, IL-1 sRI, CCR7, ApoA2, ENA-78, Myosin 18B, Desmoplakin, Neurabin 1, FGF-4, PDGF-BB, PCBP2, P20Sb3, IGF2BP1, Chordin-Like 2, UNC-13 Homolog D, Enolase 2, Angiopoietin-2, TFF2(1), RHOC, SUMO3, DGK, HVEM/TNFRSF14, GRO-a, GALNT2, TECK/CCL25, Notch-1, Cystatin S, IL-2 R alpha, WNK2, eIF5A, TrypsinPan, SCF, CD30/TNFRSF8, IL-1 F6/FIL1 epsilon, CutA, CFL1, TRAIL R4/TNFRSF10D, MBD2, UBE2N/Ubc13, PI 16, DANCE, FABP2, IGFBP-4, NEP, NRG1 Isoform GGF2, IL-2 R gamma, MAC-1, MPO, SerpinE2, GDF1, IL-17, Orexin A, Kremen-1, Smad 4, IL-17B R, GCSF, Annexin V, IL-31, TRAP1, Transketolase/TALDO, pIgR, Brg1, BMX, MAN1, Orosomucoid 2, RAPIAB, VEGF-B, SLC38A10, RPS2, RANTES, SerpinB4, Nestin, Complement factor H, MAPRE1, PDGF-AA, Reg1A, MUCDHL, SSTR2, IGSF4B, TSG-6, Orexin B, Quiescin Q6, IGFBP-2, IGFBP-rp1/IGFBP-7, Dystroglycan, Alanine Transaminase/ALT, FKBP12, Growth Hormone R (GHR), MCP-1, IL-21, RANK/TNFRSF11A, HRG-beta 1, ACTC1, Ribonuclease T2, B3GNT1, Src(1), PCYOX1, Leptin R, IL-19, CXCR1/IL-8 RA, PTP mu, IL-1 ra, PDGF-D, HEXB, ERp57, PLC-gamma 1, Nesprin2, Frizzled-4, B7-H2, NAGLU, Serpin B5, TNF RI/TNFRSF1A, IL-1 F9/IL-1 H1, Histone H2B K, OX40 Ligand/TNFSF4, Aminoacylase, Transaldolase 1/TALDO1, Glucagon, IFRD1, sFRP-4, IL-22, Kininostatin/kininogen, PRDM13, CCR5, C 1q, AMPKa1, EXTL2, POR, Smad 8, TXNDC5, IL-17RD, TREM-1, SDNSF, FKBP51, Complement Factor B, Cadherin-6, VCAM-1 (CD106), 11b-HSD1, Tie-1, Vimentin B, DISC 1, RPL7A, GDF-15, IL-31 RA, IL-5 R alpha, p16 ARC, EN-RAGE, Biglycan, DSCAM, Aggrecan, DCI, Cathepsin A, HGFR, sFRP-1, IL-4 R, IL-5, FGF R3, Activin RIA/ALK-2, Prdx6, Cathepsin L, Ezrin, TAX1BP3, FGF-BP, AMICA, KMD4B, Artemin, Axl, Claudin-4, SDF-1/CXCL12, FADD, MAP1A, ABCF1, Annexin A6, G-CSF R/CD 114, TSLP R, BRCA 2, EphA2, Cystatin SN, Fas Ligand, Pappalysin-1, ME1, 2B4, Fc RI1B/C, Dkk-4, alpha-Synuclein, Neural Cadherin, ANGPTL3, C1q S, ATBF1/ZFHX3, IGF-I, IL-3, IL-3 R alpha, Semaphorin 6B, DPPIV, LAMP2, Angiopoietin-like 1, ERAP2, PCDX8, ALKP, TMEFF2, IFN-alpha/beta R2, STOM, HSP20, Ck beta 8-1, IL-2 R beta/CD122, NrCAM, MMRN1, OSCAR, IL-21 R, PTMA, BLMH, PLS3, IL-10, CPM, cIAP-2, Pref-1, GASP-1/WFIKKNRP, FAP, Fibrinogen, PPCS, LFA-1 alpha, Mcl-1, DcR3/TNFRSF6B, Mesothelin, TACT/TNFRSF13B, Chemerin, WISP2, GM-CSF, DLL4, TLS/FUS, AGA, BTC, Chromogranin B, HMGB3, CFVII, Cryptic, CCR6, CrkL, 14-3-3 beta, TGF-beta RI/ALK-5, EphA1, Trypsin 1, Lipocalin-1, Podocalyxin, sgp130, Lipocalin-2, Caspase-3, ITIH4 a, FSH, Ras, PTP kappa, TIMP-1, Calsyntenin-1, MARCKS, ARP19, Fibronectin, Activin RIB/ALK-4, Chitobiase, OSBP1, IL-23, IL-12 R beta 1, GCSH, PLOD2, Nectin-3, GRP75, Soggy-1, MIP-3 alpha, GFR alpha-4, HMGB1, PCK2, LRP-1, MMP-8, HSP70, EPCR, Epiregulin, Gasl, CTLA-4/CD152, IL-27, TGF-beta 1, Attractin, BNIP2, BMP-5, PKLR, CCR3, Histone H2A, PDGF-C, IL-17B, Osteoactivin/GPNMB, CPE, CD40/TNFRSF5, CA1, Triosephosphate isomerase/TPIS, ADAMTS-17, EYA2, GFR alpha-1, Amylin, DMP-1, NUP98, SERPING1, CKB, CCR2, pro-MMP13, ApoC1, Glucose 6 Phosphate Dehydrogenase/G6PD, Caldesmon/CALD1, TLR2, NGF R, PSA-Free, COCO, MRP 1, MCAM, GRP78, IL-9, IL-1 R9, NAIP, RBP4, PABP, CEACAM-1, ADAMTS-5, ALPP, GPX1, Cathepsin X/Z/P, ApoB, Contactin-2, LRP-6, MMP-2, MFRP, Survivin, Siglec-1, PD-ECGF, cTnT, Thioredoxin-1, PGD, RPS23, TPX, LAMP, Myotrophin, SSTR5, IP-10, PGRPL, GDF7, FAM20C, ARFBP1, Activin RIIA, Sonic Hedgehog (Shh N-terminal), ApoC2, CFI, Adipsin, C7, ApoM, HRG, Fibulin 3, HINT1, GPBB, GDF5, Histone H1.3, RELM beta, glutathione S transferase Omega 1/GSTO1, Serpin A3, ErbB2, XIAP, IBSP, MICA, Desmocollin-3, Prolactin, Leptin (OB), WISP-1/CCN4, Aldolase B, NPAS3, LOX-1, hnRNP G, PACS1, BIK, Glycerol 3 Phosphate Dehydrogenase, Olfactomedin-2, GFR alpha-2, MSH6, ANGPTL4, Prouroguanylin, PHAP1, FKBP25, BMP-8, CFHR 1, Osteocalcin, HBZ, HOXD11, LEDGF, NeuroD1, RanGAP1, NF-M, SOX17, PYY, IL-20, Cytochrome c, IL-15, CA 15-3, Hemoglobin, DCBLD2, Serpin I1, DLL1, FGF-21, RNASE6, Annexin A7, PCCA, GLIPR2, Desmuslin, C9, Proteasome 20S b7, ARX, LIF R alpha, Cis, Chymase, Prion protein PrP/PRNP, IFN-gamma, CNOT1, UROD, IL-1 R6/IL-1 Rrp2, PER1, CFHR2, Thymidine Kinase-1, PTP gamma, LBP, BCAM, NM23-H1/H2, Lysozyme, Frizzled-5, PARC/CCL18, ROR1, Serpin A8, Persephin, IL-13 R alpha 1, IGFBP-3, Neurturin, perilipin 3, PSMB5, PLUNC, Cathepsin G, Siglec-9, MMP-15, Frizzled-7, ARB1, CL-P1, Glypican 3, MFG-E8, GATA-3, Frizzled-6, beta B1 Crystallin/CRYBB1, Siglec-5/CD170, TOPORS, PIN, Hemoglobin A1c, S100A8, EphB4, CLC, Cystatin A, Transthyretin, GSR, GAPDH, Trappin-2, Plastin L, PSMA1, Cathepsin S, IGFBP-5, LILRA3, GITR Ligand/TNFSF18, KRT31, KCTD10, BTD, LYVE-1, ACE, ECM-1, ZNF671, FoxP3, ROBO4, Cystatin C, BIRC6, Vitronectin, beta-Catenin, beta-I Tubulin, E-Cadherin, IL-1 sRII, Plectin, Spinesin, Endorepellin, Glut2, Insulin R, Serpin D1, Azurocidin, RPS10, Catalase, Glut5, HAI-2, FGFR1 alpha, S100A4, ARPC3, Properdin, Glyoxalase ITI, Netrin-4, FABP3, ZBTB4, LIMPII, Neuritin, BMP-3b/GDF-10, Vasorin, Cortactin, Cystatin D, Smad 1, MCP-4/CCL13, Syndecan-1, Osteopontin, ApoE, APN, IFN-alpha/beta RI, Fas/TNFRSF6, Erythropoietin, ApoB100, Cathepsin H, TWEAK/TNFSF12, Chordin-Like 1, Pentraxin3/TSG-14, AFP, CD61, Cathepsin D, DOTIL, Desmocollin-2, URB, PRSS3, MASP3, ADAMTS-19, Ephrin B1, TGF-beta 3, ApoH, ALDH1A1, Nectin-1, GFAP, KLK-B1, Secretogranin V/SCG5, Peroxiredoxin 3, EphB6, MYHC, NABC1, PSMD1, AgRP, IL-23 R, Galanin, PIK3IP1, IL-1 F10/IL-1HY2, IL-28A, SOX4, ANK, PON1, Uromodulin, PPOX, Histone H4, Metallothionein, FOLR3, Neurokinin-A, Protein p65, IL-33, HDGF, APLP-1, Frizzled-3, PGRP-S, SOD4, SERPINB1, Tenascin C, GMF beta, Fyn, HPR, Neuropilin-2, Lamin A+C, ZC3H4-N-t, GSTP1, PON2, DCXR, GRO, Hornerin, COX-2, S100A10, 53BP1, PKM2, 5-100b, Lamin B1, PZP, Chitotriosidase, Osteocrin, PlGF, LOK, ALBUMIN, SHANK1, TLR1, HADHA, ApoD, PA2G4, KIF3B, Ubiquitin+1, TXNRD2, Eotaxin/CCL11, HCFC1, IL-20 R beta, Pancreastatin, FGF-10/KGF-2, Brevican, CES1, TIMP-2, MMP-10, CD30 Ligand/TNFSF8, GIP, Kallikrein 10, Ficolin-3, HNF-3 alpha/FoxA1, Thyroglobulin, TFPI, ICAM-3 (CD50), RPL14, S100A9, CA2, Hoxb3, Serpin A9, IL-20 R alpha, TFF1, Pro-BDNF, NCAM2, NPTXR, Guanylin, ALP, TMEFF1/Tomoregulin-1, PSA-total, KIAA1468, IL-7 R alpha, HSP10, GASP-2/WFIKKN, SLPI, Neogenin, Cerberus 1, PSMA7, Beta Defensin 4, FIH, CHC17, Semenogelin I/SEMG1, hHR23b, Proteasome 20S alpha, Histone H3.3, SOST, EV15L, Fetuin A, Fetuin B, GULPI/CED-6, WIF-1, GDF3, INSL3, APC, TSLP, ROCK1, TRA-1-60, HOXA10, MYH7, ACLY, EVC2, CTGF/CCN2, TRA-1-81, 14-3-3 sigma, NELL2, Ferritin, Cytochrome C, B3GNT2, Fibrinopeptide A, PISD, SAMSN1, Glut3, HSP40, PD-1, PDGF R beta, SNCG, ROCK2, CRTH-2, MP1, CD200, PDIA6, Grb2, CNTF R alpha, F11, Frizzled-1, BMP-9, ROR2, L-Selectin (CD62L), Clusterin, AKR1C3, NCAM-1/CD56, S100P, COMP, FGFR1, PARK7, Laminin 2 alpha, P1 3-Kinase C2 beta, IRE1, Filamin B, NT5C3, Lumican, FGFR2, AIF, IL-34, Multimerin 2, Latent TGF beta bp2, ADM, Inhibin beta, FOLR1, SET, Progranulin, RELM alpha, Endothelin Receptor A, FABP4, PPP2R5C, ApoE3, MN1, RPS12, MLCK, INSRR, 14-3-3 epsilon, HP1BP3, Perilipin-1, Furin, ABL1, Mannosidase II, IL-17E, Grainyhead-like protein 1 homolog/GRHL1, Neurotrimin, CLIC1, LOXL1, 14-3-3 theta, RhoGDI, ACTH, Afamin, FBPase 1, Plasminogen, Kallikrein 11, Desmoglein-1, Myoglobin, Contactin-4, PECAM-1/CD31, ADHIC, ATPSO, and any combination thereof.

In further aspects of the instant disclosure, the exosome composition may comprise an ECM component at a concentration at least 20 times the concentration of the ECM component in a comparable exosome preparation. For example, the exosome composition may comprise an ECM component at a concentration at least 20 times the concentration of the ECM component in a comparable exosome preparation and may be selected from the group consisting of: Cysteine-rich Protein 1, PIM2, Cadherin-13, Beta IG-H3, EG-VEGF/PK1, Cyclophilin A, Dkk-3, BMP-3, QDPR, PAM, EDAR, EGF R/ErbB1, ALCAM, CXCR3, SBP-1, BCMA/TNFRSF17, CCL28/VIC, IL-29, HSP47, VE-Cadherin, 1-309, TGF-beta RITI, CCR8, Fractalkine, TCN1, RSU1, uPAR, VEGF-D, PRELP, TGF-beta RII, Thrombopoietin (TPO), Endothelin, S100A6, Angiogenin, TIMP-4, MSP alpha Chain, Activin A, DMGDH, Serpin B8, TRAIL R3/TNFRSF10C, CFHR5, Caspase-14, PRDX 1, FGF-12, CXCR5/BLR-1, Semaphorin 7A, SPINK7, NT-4, TNF RII/TNFRSF1B, 6Ckine, SerRS, Angiostatin, Angiopoietin-like Factor, B7-1/CD80, Protein C, Tcf20, TROY/TNFRSF19, EMAP-II, CSH1, TLR4, RPLP0, ErbB3, RPL11, PGK-1, FGF-16, Plakophilin 1, PRCP, RAGE, Insulin, TSR2, NT-3, USP14, VDAC1/Porin, Proteasome 20S a+b, M-CSF, IL-2, ICAM-1, NEDD8, PRG2, Insulysin/IDE, ICAM-2, MMP-1, Salivary alpha amylase/aAmylase, IL-17F, Galectin-1, Lymphotoxin beta/TNFSF3, TBCA, PREP, VAP-A, Utrophin, YB1, VAP-1, CFHR4, FGF-20, Cyclophilin B, RNASE4, SBSN, FGF R4, FGF-17, PGLS-C-t, Eotaxin-3/CCL26, RREB1, TMEM223, ADAMTS-15, Semenogelin II/SEMG2, C3a, RPL12, GDF8, IGF-II, RPS25, Follistatin-like 1, Smad 5, Notch-2, I-TAC/CXCL11, TRANCE, MMP-3, uPA, WDR1, UQCRB, DR6/TNFRSF21, BMP-15, PSMA4, ErbB4, Gephyrin, beta-NGF, BMP-2, BMP-6, NAP-2, LECT2, FGF-13 IB, Reg3A, CD14, SHIP, RPL5, VEGF, IL-1 F5/FIL1delta, RPS28, TUBA6, Endostatin, MMP-9, CK-MB, CapG, IL-11, Ribonuclease A, Eotaxin-2/MPIF-2, GLO-1, TLR3, HGF, Sterol carrier protein 2/SCP2, Visfatin, SHC1, IL-18 R beta/AcPL, SIGLEC14, PRTN3, Contactin-1, CV-2/Crossveinless-2, EDG-1, CXCL14/BRAK, TIMP-3, Serpin A1, Annexin A1, TGM3, CXCR6, PGM1, Osteoprotegerin/TNFRSF11B, Coagulation Factor III/Tissue Factor, M-CSF R, MDC, FAM3B, MMP-11/Stromelysin-3, SCF R/CD117, TGF-beta 5, Titin, sFRP-3, IL-1 beta, HCC-4/CCL16, TRAIL/TNFSF10, Fascin, BNP, ADAMTS-13, PLOD1, FLRG, LDHA, LIF, YY1, NME3, ESAM, RPS19, EpCAM, TAGLN2, CXCL16, BTF3, Hemoglobin subunit beta/HBB, TRADD, Metavinculin, BDNF, Galectin-7, PPP2R4, FACX, PDZD2, IL-26, FGF-9, Fibrinogen-like 2, Plexin B2, Thrombomodulin, Dtk, TRAIL R2/DR5/TNFRSF10B, PNP, ANGPTL8, B7-H3, ACLP, Galectin-3, p73, IL-4, IL-13 R alpha 2, TOB2, Claudin-3, IL-8, VEGF-C, IGF-1 SR, Tenascin X(1), Lefty-A, Thrombospondin-1, OSM R beta, SUCLG1, PDGF-AB, IL-6 R, IL-18 BPa, PGAM2, Cripto-1, FGF-23, GSTM1, ICAM-5, RPL10, Ribonuclease Inhibitor, ARTS1, Periostin, UCH-L1, Zyxin, RPLI0A, PDLIM5, IL-15 R alpha, FAM3C, Tropomyosin 3, LZTS1, LIGHT/TNFSF14, Osteoadherin(2), SHMT1, CCR9, TWEAK R/TNFRSF12, TPP1, ADAMTS-10, RCL, PCDH7, MIG, SPARC, SH3BGRL, Thrombospondin-4, UFM 1, Prostaglandin D Synthase/PTGDS, GPR-39, SPTBN1, BLVRB, RKIP, 4-1BB, Decorin, CRIM 1, PCSK9, STI1, IL-22 BP, VEGF R2 (KDR), Ficolin-2, CXCR4 (fusin), SIGIRR, IFN-beta, Cyclin D1, MIP-1a, RPS11, Alpha 1 AG, BLAME, Cystatin E/M, GM-CSF R alpha, Uteroglobin(1), Trypsinogeb-2, MCP-3, Erythropoietin R, Proteasome subunit alpha type 6/PSMA6, TGF-alpha, FIt-3 Ligand, Nanog, TNF-alpha, Spectrin beta-5, VNN1, BMP-1, FGF-7/KGF, OSM, FGF R5, and Transferrin.

In various aspects, the concentration of the ECM component may be at least 30 times the concentration of the ECM component in a comparable exosome preparation. In some aspects, the ECM component may be selected from the group consisting of Cysteine-rich Protein 1, PIM2, Cadherin-13, Beta IG-H3, EG-VEGF/PK1, Cyclophilin A, Dkk-3, BMP-3, QDPR, PAM, EDAR, EGF R/ErbB1, ALCAM, CXCR3, SBP-1, BCMA/TNFRSF17, CCL28/VIC, IL-29, HSP47, VE-Cadherin, 1-309, TGF-beta RIII, CCR8, Fractalkine, TCN1, RSU1, uPAR, VEGF-D, PRELP, TGF-beta RII, Thrombopoietin (TPO), Endothelin, S100A6, Angiogenin, TIMP-4, MSP alpha Chain, Activin A, DMGDH, Serpin B8, TRAIL R3/TNFRSF10C, CFHR5, Caspase-14, PRDX 1, FGF-12, CXCR5/BLR-1, Semaphorin 7A, SPINK7, NT-4, TNF RII/TNFRSF1B, 6Ckine, SerRS, Angiostatin, Angiopoietin-like Factor, B7-1/CD80, Protein C, Tcf20, TROY/TNFRSF19, EMAP-II, CSH1, TLR4, RPLP0, and ErbB3.

In still other aspects, the concentration of the ECM component is at least 40 times the concentration of the ECM component in a comparable exosome preparation comprising an intact extracellular matrix. For example, the ECM component may be selected from the group consisting of Cysteine-rich Protein 1, PIM2, Cadherin-13, Beta IG-H3, EG-VEGF/PK1, Cyclophilin A, Dkk-3, BMP-3, QDPR, PAM, EDAR, EGF R/ErbB1, ALCAM, CXCR3, and SBP-1.

In still other aspects, the concentration of the ECM component may be at least 50 times the concentration of the ECM component in a comparable exosome preparation. For example, the ECM component may be selected from the group consisting of Cysteine-rich Protein 1, PIM2, Cadherin-13, Beta IG-H3, EG-VEGF/PK1, and Cyclophilin A.

In any of the above or foregoing aspects, the exosome composition may be compared to a comparable exosome preparation, wherein the comparable exosome preparation is an exosome preparation prepared via ultra-centrifugation.

In any of the above or foregoing aspects, the exosome composition may comprise 1 billion or more exosomes.

Also provided in various aspects of the present disclosure is an MSC composition comprising one or more mesenchymal stem cells. In some aspects, the MSC composition is free of extracellular matrix colonies fragments thereof.

In various aspects, the exosome composition and/or the MSC composition disclosed herein may further comprise a carrier or excipient.

In another aspect of the present disclosure, a method for preparing an exosome composition and an MSC composition is provided, the method comprising: (a) culturing mesenchymal stem cells isolated from a tissue sample in an exosome collection media, (b) collecting the exosome collection media as a first fraction and the mesenchymal stem cells as a second fraction, the second fraction further comprising exosomes and extracellular matrix colonies and fragments thereof, (c) filtering the second fraction through a first section of a tangential flow filtration system to obtain a retentate comprising mesenchymal stem cells and a first filtrate comprising exosomes and the extracellular matrix colonies and fragments thereof (d) collecting the retentate comprising mesenchymal stem cells as a MSC composition, (e) filtering the first filtrate through a second section of the tangential flow filtration system to form a second retentate comprising the and the extracellular matrix colonies and fragments thereof and a second filtrate comprising exosomes and at least one component from the extracellular matrix, (f) combining the second filtrate with the first fraction to form a third fraction, and (g) collecting the third fraction as the exosome composition.

In some aspects, the method may comprise filtering the third fraction through a third section of the tangential flow filtration system to form a third filtrate and collecting the third filtrate as the exosome composition. In some aspects, the third filtrate may comprise at least one component from the extracellular matrix, an “ECM component”, wherein the ECM component is present at a higher concentration in the third filtrate than in the third fraction.

In still further aspects, the method may comprise filtering the third filtrate through a fourth section of the tangential flow filtration system to form a fourth filtrate and collecting the fourth filtrate as the exosome composition. The fourth filtrate may comprise at least one component from the extracellular matrix, an “ECM component”, wherein the ECM component is present at a higher concentration in the fourth filtrate than in the third filtrate.

In any of the filtering methods described herein, the first section of the tangential flow filtration system may comprise a filter having a pore size of about 50 kD to about 100 microns. In some aspects, the second section of the tangential flow filtration system can comprise a filter having a pore size of about 50 kD to about 100 microns. In some aspects, the third section of the tangential flow filtration system can comprise a filter having a pore size of about 50 kD to about 100 microns. In various aspects, the fourth section of the tangential flow filtration system can comprise a filter having a pore size of about 50 kD to about 100 microns.

In any of the methods of preparing the exosome or mesenchymal stem cell compositions herein, the tissue sample may comprise or be obtained from umbilical cord blood, placental tissue, umbilical cord tissue, adipose tissue, bone marrow, skin, ocular tissue, or teeth.

Also provided are an exosome composition prepared by any method described herein.

Further aspects of the present disclosure are directed to a mesenchymal stem cell composition prepared by a method described herein.

Another aspect of the present disclosure is directed to a kit comprising (a) an exosome composition described herein and/or prepared according to any method described herein; (b) a mesenchymal stem cell composition described herein and/or prepared according to any method described herein; or (a) and (b). In some aspects, the kit comprises (a) an exosome composition described herein and/or prepared according to any method described herein. In some aspects, the kit comprises (b) a mesenchymal stem cell composition described herein and/or prepared according to any method described herein. In some aspects, a kit provided herein comprises a) an exosome composition described herein and/or prepared according to any method described herein and (b) a mesenchymal stem cell composition described herein and/or prepared according to any method described herein.

Another aspect of the present disclosure is directed to a method of treating a subject in need thereof, the method comprising administering any exosome composition described herein and/or prepared according to any method herein, and at least one mesenchymal stem cell (e.g., in a mesenchymal stem cell composition described herein) to the subject.

BRIEF DESCRIPTION OF THE DRAWINGS

The foregoing and other objects of the present disclosure, the various features thereof, as well as the disclosure itself may be more fully understood from the following description, when read together with the accompanying drawings in which:

FIG. 1 is a flow chart delineating the steps (bolded) of the method according to one embodiment of the disclosure.

FIG. 2A is a representation of a flow cytometry plot of control MSCs (control).

FIG. 2B is a representation of a flow cytometry plot of single MSCs from an umbilical cord tissue.

FIG. 2C is a representation of a flow cytometry plot of live MSCs from umbilical cord.

FIG. 2D is a representation of a flow cytometry plot of a subset of umbilical cord MSCs expressing HLA-DR and CD34

FIG. 2E is a representation of a flow cytometry plot of a subset of CD20 and CD45-expressing MSCs from umbilical cord.

FIG. 2F is a representation of a flow cytometry plot of a subset of umbilical cord MSCs expressing CD90.

FIG. 2G is a representation of a flow cytometry plot of CDIOS-expressing cells from an umbilical cord sample.

FIG. 3A is a representation of a flow cytometric plot of a sample of umbilical cord MSCs.

FIG. 3B is a graphic representation of counts reflecting the presence of CD20-expressing exosomes from the MSC sample shown in FIG. 3A.

FIG. 3C is a graphic representation of counts reflecting the presence of CD34-expressing exosomes from the MSC sample in FIG. 3A.

FIG. 3D is a graphic representation of counts reflecting the presence of CD45-expressing exosomes from the MSC sample in FIG. 3A.

FIG. 3E is a graphic representation of the counts reflecting the presence of CD73-expressing exosomes from the MSC sample in FIG. 3A.

FIG. 3F is a graphic representation of counts reflecting the presence of CD90-expressing exosomes from the MSC sample in FIG. 3A.

FIG. 3G is a graphic representation of counts reflecting the presence of CD105-expressing exosomes from the MSC sample in FIG. 3A.

FIG. 3H is a graphic representation of counts reflecting the presence of CD166-expressing exosomes from the MSC sample in FIG. 3A.

FIG. 3I is a graphic representation of counts reflecting the presence of HLA-DR-expressing exosomes from the MSC sample in FIG. 3A

DETAILED DESCRIPTON

In various aspects, the present disclosure is directed to therapeutic compositions comprising at least one exosome (e.g., as isolated from a mesenchymal stem cell), and at least one extracellular matrix component (ECM component) wherein the composition does not comprise an intact extracellular matrix. Methods of preparing these therapeutic compositions and exemplary therapeutic uses are also provided herein.

I. Compositions

In one aspect of the disclosure, an exosome composition is provided comprising at least one exosome isolated from a mesenchymal stem cell, and at least one component isolated from an extracellular matrix (e.g., an “ECM component”). In another aspect of the disclosure, an MSC composition is provided comprising at least one mesenchymal stem cell, wherein the MSC composition is free of any extracellular matrix or fragments thereof. Advantageously, the exosome compositions herein do not comprise any intact extracellular matrix (for example, ECM that is in contact with the mesenchymal stem cell). Also advantageously, the present compositions derive their therapeutic benefits without genomic modifications (e.g., without incorporating gene edited cells) and without subjecting the mesenchymal stem cells to stressful conditions (e.g., hypoxia). In various aspects, the exosome composition and the MSC composition provided herein are each prepared from a single tissue sample using a process comprising tandem tangential flow filtration.

Mesenchymal Stem Cells

Mesenchymal stem cells (MSCs) are highly proliferative, multipotent cells that can be isolated from umbilical cord tissue or blood, placental tissues, bone marrow, skin, and fat and can differentiate into mesenchymal cells with negligible risk of teratoma formation. These cells secrete exosomes which are nanoparticles or extracellular vesicles of about 30 nm to 250 nm in diameter.

Extracellular Matrix

The extracellular matrix (ECM) is secreted by cells and surrounds them in tissues. Its purpose is to be the structural support for cells since its characteristics determine the characteristics of the tissue (bone compared to cartilage to organs). ECM is not passive mechanical support for cells. It in fact an incredibly complex scaffold composed of a variety of biologically active molecules that are highly regulated and critical for determining the action and fate of the cells that it surrounds.

ECM proteins (growth factors, cytokines, peptides, poly peptides etc. . . . ) play crucial and complex roles during cell surface receptor signaling. ECM serves as a reservoir for growth factors, allowing for their local release and association with their canonical receptors. Many ECM proteins have binding sites for both cell adhesion and growth factors, allowing local concentration of the growth factors near to their cell surface receptors and cell adhesion sites. This localization of growth factors, and thus their signaling, by the ECM probably contributes to the establishment of gradients of the soluble, diffusible growth factor morphogens, which play vital roles in patterning in developmental processes.

The two basic constructs of the Extracellular Matrix are the basement membrane and the interstitial matrix. The baement membran encompasses the ECM between and around the epithelial and stromal layers of cells. The ECM is produced by epithelial cells and stromal cells found within the matrix itself, including fibroblasts, osteoblasts, and basal epithelial cells. It provides mechanical structure, separates different cell types and signals for cell differentiation, migration and survival. The ECM also provides much of the structural support available to parenchymal cells in tissues. This provides tensile strength and flexibility. The interstitial matrix is a type of extracellular matrix found in between various animal cells in the intercellular space. It is characterized by the presence of fibronectins and types I, III, V, VI, VII and XII collagens. ECM surrounding cells forms a porous 3D lattice and the interstitial matrix acts as a compression buffer against stress placed on the ECM.

The ECM is a complex mixture of proteins and glycosoaminoglycans (negatively charged polysaccharides) and generally contains three categories of materials: (a) glyocosaminoglycans and their proteoglycans which resist compressive forces, (b) adhesive glycoproteins and (c) fibrous proteins that provide tensile strength. Each are described further below.

(a) Glycosaminoglycans (GAGs).

Glycosaminoglycans (GAGs) are linear polysaccharides composed of two basic saccharides: an amino sugar and an uronic acid. The origin of the ECM determines the carbohydrate chain and the other chemical modifications that determine their specificity and functionality. GAGs were originally primarily known for being “space fillers” in the ECM. More recently they have been shown to be active signaling molecules whose roles in a variety of cellular processes (including cytokine production, leukocyte recruitment and inflammatory response) are important for controlling cell fate. There are four classes of glycosaminoglycans: (1) hyaluronan, (2) chondroitin sulfate (CS)/dermatan sulfate (DS), (3) heparan sulfate (HS)/heparin, and (4) keratan sulfate (KS). Hyaluronan is a naturally occurring biopolymer possessing numerous functions within the body including wound facilitation, cell migration, and cell signaling. Hyaluronan is an extremely versatile material with various unique properties. Commonly excreted by cells such as fibroblasts and chondrocytes, Hyaluronan is an important part of the extracellular matrix and also functions in cell signaling and wound repair8. Hyaluronan is composed of multiple negatively charged hyaluronic acid subunits, allowing it to attract and retain water. The binding of water provides support to the extracellular matrix and allows for compressibility and tensile strength. The other GAGs are chondroitin sulfate (CS), dermatan sulfate (DS), keratan sulfate (KS), and heparan sulfate (HS). These four GAGs are typically covalently attached to proteins to form proteoglycans.

Related to glycosaminoglycans are proteoglycans. A proteoglycan is composed of a core protein with one or more covalently attached GAGs. They are stored in secretory granules, inserted into the plasma membrane or secreted into the ECM.

(b) Adhesive Glycoproteins

Various adhesive glycoproteins are included in extracellular matrices—including laminin, fibronectin and integrins, described below.

Laminin. Laminins are the most abundant glycoproteins of the basement membrane extracellular matrix (ECM) and can be found in almost all tissues of the body. Laminin is composed of α, β, and γ chains of which there are 5α, 4β, and 6γ chains. It has a cross-like structure with 3 short arms and 1 long arm. The α chains possess a large globular domain known as the G domain at the C-termini. Laminin, as a key component of the basement membrane extracellular matrix (ECM), regulates tissue morphogenesis. Laminin supports growth and differentiation of many cell types including epithelial, endothelial, neural, muscle and organ cells. They play essential roles in the establishment of tissue architecture and stability and provide cells with a structural scaffold. As such, laminins are involved in a variety of biological processes ranging from tissue survival, angiogenesis¹³, and neural development, to skin re-epithelialization and wound healing. Laminins have been shown to regulate core cellular activities, such as adhesion, apoptosis, proliferation, migration, and differentiation.

Fibronectin. Fibronectin (FBN) is a high-molecular weight glycoprotein of the extracellular matrix. FBN is an ECM component that, through binding integrin receptors of the cell surface, acts as a key player of the communication between the intra and the extracellular environment, thus controlling cell behavior. It binds collagen, heparin, other fibronectin proteins, and cell surface integrins. Fibronectin binds integrins through the tri-peptide motif of arginine, glycine, and aspartic acid.

Integrins. Integrins are the main cell adhesion receptors involved in focal adhesion formation and are required for cell migration. Cells respond to the mechanical and biochemical changes in ECM through the crosstalk between integrins and the actin cytoskeleton. Integrins are heterodimeric transmembrane receptors composed of eighteen a subunits and eight b subunits that can be non-covalently assembled into 24 combinations. The integrin dimers bind to an array of different ECM molecules with overlapping binding affinities. Therefore, the specific integrin expression patterns by a cell dictate which ECM substrate the cell can bind and the composition of integrin adhesomes determines the downstream signaling events, thus the eventual cell behavior and fate. Integrins have unique ability to respond to the molecular composition and physical properties of the ECM and integrate both mechanical and chemical signals through direct association with the cytoskeleton, which also determines the selection of specific integrin species to be involved.

ECM further comprises various fibrous proteins that provide tensile strength. Exemplary fibrous proteins are collagen and elastin, discussed below.

Collagens. Collagens are the major structural component of the ECM. Collagens provide scaffolding for the attachment of laminin, proteoglycans and cell surface receptors. Twenty-eight types of collagens (I-XXVIII) with multiple sub types have been identified so far in the ECM. Collagens play structural roles and contribute to mechanical properties, organization, and shape of tissues. They interact with cells via several receptor families and regulate their proliferation, migration, and differentiation. Collagens are deposited in the extracellular matrix where most of them form supramolecular assemblies (e.g., fibrillar, fibril-associated, beaded filament, network-forming, or transmembrane collagens). Fibrillar assemblies, formed from types I, II, III, V, XI, XXIV, and XXVII collagens, are the most comment type of assemblies—accounting for 90% of the collagen in the body and concentrated in healthy bone, skin, tendons, ligaments and cartilage. Fibril-associated (FACIT) collagens (IX, XII, XIV, XVI, XIX, XX, XXI, XXII) do not form fibrils, but do attach to fibril forming collagens. This group is thought to serve as molecular bridges important for organization and stability of extracellular matrices. They reinforce and make dense connective tissues, bones, tendons, joints and ligaments. Beaded filament (VI) collagen maintains regularity in muscle function and stabilizes the cell membrane. Network-forming (IV, VIII and X) form net-like structures such as the basement membrane and interact with anchoring fibrils (type VII) which link the basement membrane to collagen and laminin in the ECM. This group is essential for providing a scaffold for assembly and mechanical stability but are also important in cell adhesion, migration, survival, proliferation and differentiation. Finally, transmembrane collagens (XIII, XVII, XXIII, XXV) have a function role in cell adhesion, differentiation, tissue development and structural integrity. Accordingly, collagens may be understood to exist in a monomer or fragmented state and also in supramolecular assemblies which may or may not include fibrils.

Elastin provides elasticity to the ECM. It is produced as tropoelastin, a 72 kDa precursor protein that is secreted from the cell. In the extracellular space it crosslinks with other elastin molecules to form sheets and fibers. Elastin is a key ECM protein that provides resilience and elasticity to tissues and organs. Elastin is roughly 1000 times more flexible than collagens thus providing for its function to increase the elasticity of tissues. This is critical for organs and tissues that require elastic recoil and flexibility.

In addition to these large structural components, the extracellular matrix also contains various factors (growth factors or cytokines), signaling molecules, nucleic acids, lipids, and extra cellular vesicles (e.g., exosomes) that are valuable for cell signaling and that may be useful in various therapeutics. In various aspects of the present disclosure, it is desirable to obtain these structural components and these growth factors/signaling molecules and vesicles and isolate them from the extracellular matrix.

In various aspects, the exosome composition provided herein can comprise one or more exosomes and one or more components isolated from an extracellular matrix (e.g., one or more of the components listed above, each of which are referred to herein as an “ECM component”). The exosome composition described herein are prepared from a single tissue sample using tangential flow filtration, and preferably tandem tangential flow filtration.

In still further aspects, the exosome compositions may comprise one or more component isolated from an extracellular matrix (ECM component). In various aspects, the one or more ECM component may comprise a glycosaminoglycan or proteoglycan thereof, an adhesive glycoprotein, a fibrous protein, and a growth factor.

In various aspects, the one or more ECM component may comprise a glycosaminoglycan. In some aspects, the glycosaminoglycan is selected from the group consisting of hyaluronan, chondroitin sulfate (CS), dermatan sulfate (DS), keratan sulfate (KS), and heparan sulfate (HS), or any proteoglycan thereof.

In various aspects, the one or more ECM component may comprise an adhesive glycoprotein. In various aspects, the adhesive glycoprotein is selected from the group consisting of Laminin, Fibronectin, tenascin, and nidogen.

In various aspects, the one the one or more ECM component may comprise a fibrous protein. The fibrous protein may, in some aspects, be selected from the group consisting of collagens and elastin.

In various aspects, the one or more ECM component may comprise a growth factor. Suitable growth factors that may be included in the exosome composition include, but are not limited to EGF, Endothelin, Eotaxin/CCL11, FGF-4, GDF-15, ICAM-1, IGFBP-1, IL-6, PDGF-AA, TGF-beta 3, TIMP-1, TIMP-2, BCAM, Smad 4, CD 163, CD30 Ligand, TNFSF8, and Integrin b1.

In various aspects, the one or more ECM component may be selected from any one of Cysteine-rich Protein 1, PIM2, Cadherin-13, Beta IG-H3, EG-VEGF/PK1, Cyclophilin A, Dkk-3, BMP-3, QDPR, PAM, EDAR, EGF R/ErbB1, ALCAM, CXCR3, SBP-1, BCMA/TNFRSF17, CCL28/VIC, IL-29, HSP47, VE-Cadherin, I-309, TGF-beta RIII, CCR8, Fractalkine, TCN1, RSU1, uPAR, VEGF-D, PRELP, TGF-beta RII, Thrombopoietin (TPO), Endothelin, S100A6, Angiogenin, TIMP-4, MSP alpha Chain, Activin A, DMGDH, Serpin B8, TRAIL R3/TNFRSF10C, CFHR5, Caspase-14, PRDX 1, FGF-12, CXCR5/BLR-1, Semaphorin 7A, SPINK7, NT-4, TNF RII/TNFRSF1B, 6Ckine, SerRS, Angiostatin, Angiopoietin-like Factor, B7-1/CD80, Protein C, Tcf20, TROY/TNFRSF19, EMAP-II, CSH1, TLR4, RPLP0, ErbB3, RPL11, PGK-1, FGF-16, Plakophilin 1, PRCP, RAGE, Insulin, TSR2, NT-3, USP14, VDAC1/Porin, Proteasome 20S a+b, M-CSF, IL-2, ICAM-1, NEDD8, PRG2, Insulysin/IDE, ICAM-2, MMP-1, Salivary alpha amylase/aAmylase, IL-17F, Galectin-1, Lymphotoxin beta/TNFSF3, TBCA, PREP, VAP-A, Utrophin, YB1, VAP-1, CFHR4, FGF-20, Cyclophilin B, RNASE4, SBSN, FGF R4, FGF-17, PGLS-C-t, Eotaxin-3/CCL26, RREB1, TMEM223, ADAMTS-15, Semenogelin II/SEMG2, C3a, RPL12, GDF8, IGF-I1, RPS25, Follistatin-like 1, Smad 5, Notch-2, I-TAC/CXCL11, TRANCE, MMP-3, uPA, WDR1, UQCRB, DR6/TNFRSF21, BMP-15, PSMA4, ErbB4, Gephyrin, beta-NGF, BMP-2, BMP-6, NAP-2, LECT2, FGF-13 1B, Reg3A, CD14, SHIP, RPL5, VEGF, IL-1 F5/FIL1delta, RPS28, TUBA6, Endostatin, MMP-9, CK-MB, CapG, IL-11, Ribonuclease A, Eotaxin-2/MPIF-2, GLO-1, TLR3, HOF, Sterol carrier protein 2/SCP2, Visfatin, SHC1, IL-18 R beta/AcPL, SIGLEC14, PRTN3, Contactin-1, CV-2/Crossveinless-2, EDG-1, CXCL14/BRAK, TIMP-3, Serpin A1, Annexin A1, TGM3, CXCR6, PGM1, Osteoprotegerin/TNFRSF1 IB, Coagulation Factor III/Tissue Factor, M-CSF R, MDC, FAM3B, MMP-11/Stromelysin-3, SCF R/CD117, TGF-beta 5, Titin, sFRP-3, IL-1 beta, HCC-4/CCL16, TRAIL/TNFSF10, Fascin, BNP, ADAMTS-13, PLOD1, FLRG, LDHA, LIF, YY1, NME3, ESAM, RPS19, EpCAM, TAGLN2, CXCL16, BTF3, Hemoglobin subunit beta/HBB, TRADD, Metavinculin, BDNF, Galectin-7, PPP2R4, FACX, PDZD2, IL-26, FGF-9, Fibrinogen-like 2, Plexin B2, Thrombomodulin, Dtk, TRAIL R2/DR5/TNFRSF10B, PNP, ANGPTL8, B7-H3, ACLP, Galectin-3, p73, IL4, IL-13 R alpha 2, TOB2, Claudin-3, IL-8, VEGF-C, IGF-I SR, Tenascin X(1), Lefty-A, Thrombospondin-1, OSM R beta, SUCLG1, PDGF-AB, IL-6 R, IL-18 BPa, PGAM2, Cripto-1, FGF-23, GSTM1, ICAM-5, RPL10, Ribonuclease Inhibitor, ARTS1, Periostin, UCH-L1, Zyxin, RPL10A, PDLIM5, IL-15 R alpha, FAM3C, Tropomyosin 3, LZTS1, LIGHT/TNFSF14, Osteoadherin(2), SHMT1, CCR9, TWEAK R/TNFRSF12, TPP1, ADAMTS-10, RCL, PCDH7, MIG, SPARC, SH3BGRL, Thrombospondin-4, UFM 1, Prostaglandin D Synthase/PTGDS, GPR-39, SPTBN1, BLVRB, RKIP, 4-1BB, Decorin, CRIM 1, PCSK9, STI1, IL-22 BP, VEGF R2 (KDR), Ficolin-2, CXCR4 (fusin), SIGIRR, IFN-beta, Cyclin D1, MIP-1a, RPS11, Alpha 1 AG, BLAME, Cystatin E/M, GM-CSF R alpha, Uteroglobin(1), Trypsinogeb-2, MCP-3, Erythropoietin R, Proteasome subunit alpha type 6/PSMA6, TGF-alpha, Flt-3 Ligand, Nanog, TNF-alpha, Spectrin beta-5, VNN1, BMP-1, FGF-7/KGF, OSM, FGF R5, Transferrin, C5/C5a, ApoA1, TCP1 eta, Galectin-3BP, PTPRZ, TRAIL R1/DR4/TNFRSF10A, Six3, SORD, CNTF, GDNF, BMPR-II, CXCR2/IL-8 RB, FGF-8, RPS5, CRF21, PGDF/PHGDH, FABP1, SLURP1, CEACAM-8/CD66b, UNC45A, Adiponectin/Acrp30, MMP-25/MT6-MMP, SMC4, Ornithine Carbamoyltransferase/OTC, IFN-gamma R1, CCR4, Proteasome beta 1, Talin1&2, Prohibitin, MMP-24/MT5-MMP, SP-D, Nidogen-2, PTPRS, SIRP beta 1/CD172b, APRIL, ACE-2, IL-6, HGFA, E-Selectin, GATA-4, VEGF R3, UBE2D3, BAFF R/TNFRSF13C, Layilin, Cytokeratin 8, Profilin 1, Cathepsin B, Marapsin, Lymphotactin/XCL1, Nidgen-1, MEP1A, MIF, IL-1 F8/FIL1 eta, MMP-14, HB-EGF, Latent TGF-beta bp1, C8B, SMPD4, ADAMTS-18, FGF Basic, IL-12 R beta 2, MINPP1, URP2, Glycoprotein V, LRG1, ACPP, AlphaA Crystallin/CRYAA, EDA-A2, SH3BGRL3, Serpin F2, CD40 Ligand/TNFSF5/CD154, CPEB3, A2M, Activin B, SREC-II, EGF, FGF-19, Myoferlin, Endoglin/CD105, RECK, ADAM-9, SSEA-4, DDAH1, P-Cadherin, IL-22 R, Glut1, Symplekin, SIO0A11, SLITRK1, GCP-2/CXCL6, SDPR, IGF-II R, P4HB, TNF-beta, IL-1 R8, IL-1 alpha, Angiopoietin-4, TCCR/WSX-1, GITR/TNFRFI8, ILK, TCEB2, RPL22, DEP-1, FGF-18, TL1A/TNFSFI5, EphA6, IL-36RN, Tarc, UROC1, Activin C, FASN, PYGL, Somatostatin, Musk, PLA2GIB, IL-1 R3/IL-1 R AcP, FGF-6, IL-18 R alpha/IL-1 R5, Tie-2, NIT2, PF4/CXCL4, TPM1, GDF11, IGFBP-6, Thymopoietin, FUCA1, CRHBP, C1qR1, STAT3, TPM4, Follistatin, Laminin b2, IL-1 sRI, CCR7, ApoA2, ENA-78, Myosin 18B, Desmoplakin, Neurabin 1, FGF-4, PDGF-BB, PCBP2, P20Sb3, IGF2BP1, Chordin-Like 2, UNC-13 Homolog D, Enolase 2, Angiopoietin-2, TFF2(1), RHOC, SUMO3, DGK, HVEM/TNFRSF14, GRO-a, GALNT2, TECK/CCL25, Notch-1, Cystatin S, IL-2 R alpha, WNK2, eIFSA, TrypsinPan, SCF, CD30/TNFRSF8, IL-1 F6/FIL1 epsilon, CutA, CFL1, TRAIL R4/TNFRSF10D, MBD2, UBE2N/Ubc13, PI 16, DANCE, FABP2, IGFBP-4, NEP, NRG1 Isoform GGF2, IL-2 R gamma, MAC-1, MPO, SerpinE2, GDF1, IL-17, Orexin A, Kremen-1, Smad 4, IL-17B R, GCSF, Annexin V, IL-31, TRAP1, Transketolase/TALDO, pIgR, Brg1, BMX, MAN1, Orosomucoid 2, RAP1AB, VEGF-B, SLC38A10, RPS2, RANTES, SerpinB4, Nestin, Complement factor H, MAPRE1, PDGF-AA, Reg1A, MUCDHL, SSTR2, IGSF4B, TSG-6, Orexin B, Quiescin Q6, IGFBP-2, IGFBP-rp1/iGFBP-7, Dystroglycan, Alanine Transaminase/ALT, FKBP12, Growth Hormone R (GHR), MCP-1, IL-21, RANK/TNFRSF1 1A, HRG-beta 1, ACTC1, Ribonuclease T2, B3GNT1, Src(l), PCYOX1, Leptin R, IL-19, CXCR1/IL-8 RA, PTP mu, IL-1 ra, PDGF-D, HEXB, ERp57, PLC-gamma 1, Nesprin2, Frizzled-4, B7-H2, NAGLU, Serpin B5, TNF RI/TNFRSF1A, IL-1 F9/IL-1 H1, Histone H2B K, OX40 Ligand/TNFSF4, Aminoacylase, Transaldolase 1/TALDO1, Glucagon, IFRD1, sFRP-4, IL-22, Kininostatin/kininogen, PRDM13, CCR5, C1q, AMPKa1, EXTL2, POR, Smad 8, TXNDC5, IL-17RD, TREM-1, SDNSF, FKBP51, Complement Factor B, Cadherin-6, VCAM-1 (CD106), 11b-HSD1, Tie-1, Vimentin B, DISC 1, RPL7A, GDF-15, IL-31 RA, IL-5 R alpha, p16 ARC, EN-RAGE, Biglycan, DSCAM, Aggrecan, DCI, Cathepsin A, HGFR, sFRP-1, IL-4 R, IL-5, FGF R3, Activin RIA/ALK-2, Prdx6, Cathepsin L, Ezrin, TAX1BP3, FGF-BP, AMICA, KMD4B, Artemin, Axl, Claudin-4, SDF-1/CXCL12, FADD, MAPIA, ABCF1, Annexin A6, G-CSF R/CD 114, TSLP R, BRCA 2, EphA2, Cystatin SN, Fas Ligand, Pappalysin-1, ME1, 2B4, Fc RIIB/C, Dkk-4, alpha-Synuclein, Neural Cadherin, ANGPTL3, C 1q S, ATBF1/ZFHX3, IGF-I, IL-3, IL-3 R alpha, Semaphorin 6B, DPPIV, LAMP2, Angiopoietin-like 1, ERAP2, PCDX8, ALKP, TMEFF2, IFN-alpha/beta R2, STOM, HSP20, Ck beta 8-1, IL-2 R beta/CD122, NrCAM, MMRN1, OSCAR, IL-21 R, PTMA, BLMH, PLS3, IL-10, CPM, clAP-2, Pref-1, GASP-1/WFIKKNRP, FAP, Fibrinogen, PPCS, LFA-1 alpha, Mel-1, DcR3/TNFRSF6B, Mesothelin, TACI/TNFRSF13B, Chemerin, WISP2, GM-CSF, DLL4, TLS/FUS, AGA, BTC, Chromogranin B, HMGB3, CFVII, Cryptic, CCR6, CrkL, 14-3-3 beta, TGF-beta RI/ALK-5, EphA1, Trypsin 1, Lipocalin-1, Podocalyxin, sgp130, Lipocalin-2, Caspase-3, ITIH4 a, FSH, Ras, PTP kappa, TIMP-1, Calsyntenin-1, MARCKS, ARP19, Fibronectin, Activin RIB/ALK-4, Chitobiase, OSBP1, IL-23, IL-12 R beta 1, GCSH, PLOD2, Nectin-3, GRP75, Soggy-1, MIP-3 alpha, GFR alpha-4, HMGB1, PCK2, LRP-1, MMP-8, HSP70, EPCR, Epiregulin, Gasl, CTLA-4/CD152, IL-27, TGF-beta 1, Attractin, BNIP2, BMP-5, PKLR, CCR3, Histone H2A, PDGF-C, IL-17B, Osteoactivin/GPNMB, CPE, CD40/TNFRSF5, CA1, Triosephosphate isomerase/TPIS, ADAMTS-17, EYA2, GFR alpha-1, Amylin, DMP-1, NUP98, SERPING1, CKB, CCR2, pro-MMP13, ApoC1, Glucose 6 Phosphate Dehydrogenase/G6PD, Caldesmon/CALD1, TLR2, NGF R, PSA-Free, COCO, MRP 1, MCAM, GRP78, IL-9, IL-1 R9, NAIP, RBP4, PABP, CEACAM-1, ADAMTS-5, ALPP, GPX1, Cathepsin X/Z/P, ApoB, Contactin-2, LRP-6, MMP-2, MFRP, Survivin, Siglec-1, PD-ECGF, cTnT, Thioredoxin-1, PGD, RPS23, TPX, LAMP, Myotrophin, SSTR5, IP-10, PGRPL, GDF7, FAM20C, ARFBP1, Activin RIIA, Sonic Hedgehog (Shh N-terminal), ApoC2, CFI, Adipsin, C7, ApoM, HRG, Fibulin 3, HINT1, GPBB, GDF5, Histone H1.3, RELM beta, glutathione S transferase Omega 1/GSTO1, Serpin A3, ErbB2, XIAP, IBSP, MICA, Desmocollin-3, Prolactin, Leptin (OB), WISP-1/CCN4, Aldolase B, NPAS3, LOX-1, hnRNP G, PACS1, BIK, Glycerol 3 Phosphate Dehydrogenase, Olfactomedin-2, GFR alpha-2, MSH6, ANGPTL4, Prouroguanylin, PHAP1, FKBP25, BMP-8, CFHR 1, Osteocalcin, HBZ, HOXDI 1, LEDGF, NeuroD1, RanGAP1, NF-M, SOX17, PYY, IL-20, Cytochrome c, IL-15, CA 15-3, Hemoglobin, DCBLD2, Serpin II, DLL1, FGF-21, RNASE6, Annexin A7, PCCA, GLIPR2, Desmuslin, C9, Proteasome 20S b7, ARX, LIF R alpha, Cis, Chymase, Prion protein PrP/PRNP, IFN-gamma, CNOT1, UROD, IL-1 R6/IL-1 Rrp2, PER1, CFHR2, Thymidine Kinase-1, PTP gamma, LBP, BCAM, NM23-H1/H2, Lysozyme, Frizzled-5, PARC/CCL18, ROR1, Serpin A8, Persephin, IL-13 R alpha 1, IGFBP-3, Neurturin, perilipin 3, PSMB5, PLUNC, Cathepsin G, Siglec-9, MMP-15, Frizzled-7, ARB1, CL-P1, Glypican 3, MFG-E8, GATA-3, Frizzled-6, beta B1 Crystallin/CRYBB1, Siglec-5/CD170, TOPORS, PIN, Hemoglobin A1c, S100A8, EphB4, CLC, Cystatin A, Transthyretin, GSR, GAPDH, Trappin-2, Plastin L, PSMA1, Cathepsin S, IGFBP-5, LILRA3, GITR Ligand/TNFSF18, KRT31, KCTD10, BTD, LYVE-1, ACE, ECM-1, ZNF671, FoxP3, ROBO4, Cystatin C, BIRC6, Vitronectin, beta-Catenin, beta-I Tubulin, E-Cadherin, IL-1 sRII, Plectin, Spinesin, Endorepellin, Glut2, Insulin R, Serpin D1, Azurocidin, RPS10, Catalase, Glut5, HAI-2, FGFR1 alpha, S100A4, ARPC3, Properdin, Glyoxalase II, Netrin-4, FABP3, ZBTB4, LIMPII, Neuritin, BMP-3b/GDF-10, Vasorin, Cortactin, Cystatin D, Smad 1, MCP-4/CCLI3, Syndecan-1, Osteopontin, ApoE, APN, IFN-alpha/beta R1, Fas/TNFRSF6, Erythropoietin, ApoB100, Cathepsin H, TWEAK/TNFSFI2, Chordin-Like 1, Pentraxin3/TSG-14, AFP, CD61, Cathepsin D, DOT1L, Desmocollin-2, URB, PRSS3, MASP3, ADAMTS-19, Ephrin B1, TGF-beta 3, ApoH, ALDH1A1, Nectin-1, GFAP, KLK-B1, Secretogranin V/SCG5, Peroxiredoxin 3, EphB6, MYHC, NABC1, PSMD1, AgRP, IL-23 R, Galanin, PIK3IP1, IL-1 F10/IL-1HY2, IL-28A, SOX4, ANK, PON1, Uromodulin, PPOX, Histone H4, Metallothionein, FOLR3, Neurokinin-A, Protein p65, IL-33, HDGF, APLP-1, Frizzled-3, PGRP-S, SOD4, SERPINB1, Tenascin C, GMF beta, Fyn, HPR, Neuropilin-2, Lamin A+C, ZC3H4-N-t, GSTP1, PON2, DCXR, GRO, Hornerin, COX-2, S100A10, 53BP1, PKM2, S-100b, Lamin B1, PZP, Chitotriosidase, Osteocrin, PlGF, LOK, ALBUMIN, SHANK1, TLR1, HADHA, ApoD, PA2G4, KIF3B, Ubiquitin+1, TXNRD2, Eotaxin/CCL11, HCFC1, IL-20 R beta, Pancreastatin, FGF-10/KGF-2, Brevican, CES1, TIMP-2, MMP-10, CD30 Ligand/TNFSF8, GIP, Kallikrein 10, Ficolin-3, HNF-3 alpha/FoxA1, Thyroglobulin, TFPI, ICAM-3 (CD50), RPL14, S100A9, CA2, Hoxb3, Serpin A9, IL-20 R alpha, TFF1, Pro-BDNF, NCAM2, NPTXR, Guanylin, ALP, TMEFF1/Tomoregulin-1, PSA-total, KIAA1468, IL-7 R alpha, HSP10, GASP-2/WFIKKN, SLPI, Neogenin, Cerberus 1, PSMA7, Beta Defensin 4, FIH, CHC17, Semenogelin I/SEMG1, hHR23b, Proteasome 20S alpha, Histone H3.3, SOST, EV15L, Fetuin A, Fetuin B, GULP1/CED-6, WIF-1, GDF3, INSL3, APC, TSLP, ROCK1, TRA-1-60, HOXA10, MYH7, ACLY, EVC2, CTGF/CCN2, TRA-1-81, 14-3-3 sigma, NELL2, Ferritin, Cytochrome C, B3GNT2, Fibrinopeptide A, PISD, SAMSN1, Glut3, HSP40, PD-1, PDGF R beta, SNCG, ROCK2, CRTH-2, MP1, CD200, PDIA6, Grb2, CNTF R alpha, F11, Frizzled-1, BMP-9, ROR2, L-Selectin (CD62L), Clusterin, AKRiC3, NCAM-1/CD56, S100P, COMP, FGFR1, PARK7, Laminin 2 alpha, PI 3-Kinase C2 beta, IRE1, Filamin B, NT5C3, Lumican, FGFR2, AIF, IL-34, Multimerin 2, Latent TGF beta bp2, ADM, Inhibin beta, FOLR1, SET, Progranulin, RELM alpha, Endothelin Receptor A, FABP4, PPP2R5C, ApoE3, MN1, RPS12, MLCK, INSRR, 14-3-3 epsilon, HPiBP3, Perilipin-1, Furin, ABL1, Mannosidase II, IL-17E, Grainyhead-like protein 1 homolog/GRHL1, Neurotrimin, CLIC1, LOXL1, 14-3-3 theta, RhoGDI, ACTH, Afamin, FBPase 1, Plasminogen, Kallikrein 11, Desmoglein-1, Myoglobin, Contactin-4, PECAM-1/CD31, ADHiC, ATP50, NOV/CCN3, CRTAM, Serpin B3/SCCA1, MBL, CA 125, Smad 7, Growth Hormone (GH), OX40, Serpin A5, TRP-1, PEPSINOGEN 11, PEBP4, mTOR, hnRNP L, TACE, 14-3-3 eta, IL-17C, MMP-7, Kallikrein 7, AFG3L2, VEG1/TNFSF15, APP, LAIR1, Ran, Kallikrein 14, HSP90, Nesfatin, p27, TIM-1, Pancreatic Polypeptide, MYOSA, CPNE3, Peroxiredoxin 2, Nebulin, Aldehyde Oxidase 1/AOX1, BAZ2B, Actinin alpha 1, CA3, CCT3, MMR, Progesterone, HMGB2, PDX-1, Gastrokine 1, Factor XIII, TGF-beta 2, MMP-12, Caspase-8, PSMC3, ITM2B, PDLIM1, Plexin B1, H6PD, IL-12 p70, NAPIL1, NPM1, LRP 4, Prostasin, p21, SART1, SEZ6L2, VSIG4, SEMA3A, Hemoglobin subunit gamma 2/HBG2, IL-13, ANGPTL6, NR3C3, PEDF, Livin, ABI3BP, Noelin, HTRA1, FABP5, Kremen-2, SCGF, RPS3, B4GaIT1, ACK1, APOA1BP, ADAMTS-1, THOP1, IL-7, TSH, CLIP170-N-t, EphA3, IL-24, Ntnl, Fibrinogen gamma chain/FGG, Rab7a, SIM2, Neuropeptide B, HCR/CRAM-A/B, Serpin A12, OCT3/4, FER, ITIH3, LIN41, Mer, Hepassocin, PSMD9, hnRNP A1, BCHE, Omentin, SF20, IRS2, URB2, GPX3, MMP-16/MT3-MMP, GCLC, Cytokeratin 18, FH, IL-17RC, FGF-5, GFR alpha-3, GDI2, Lamin B2, ELAVL1, UGGT, IL-17R, CTACK/CCL27, DBI, KRTDAP, SAA, MYH2, CRTAC1, HEG1, Annexin A2, P-selectin, PAI-1, Factor XIII B, Advillin-N-t, Destrin, LUZP1, Serpin A 10/ZPI, HSP32, Kallikrein 5, OIT3, Dkk-1, KRTHA3B, ENO1+ENO2+ENO3, Endocan, MSHa, AKR1B1, TXK, Pro-Cathepsin B, SOX2, JAM-A, SERTAD2, BMP-7, SPINK1, CLIC4, Human Agrin, Aldolase A, UNC5H4, GLP-1, ERRa, EphB2, C5b-9, RNA Polymerase II/POLR2A, ASPH, ANP, Antithrombin III, Cytokeratin 14, PYK2, GRP, AHNAK, hCG alpha, SorLA, EFTUD2, Endorphin Beta, Cytokeratin 17, USP5, Granzyme A, CA 9, QPRT, JARID2, S100A1, ADAMTS-L2, Pleckstrin, RELT/TNFRSF19L, IBP160, nNOS, GADD45A, C-peptide, Moesin, Hepcidin, CCR1, Pro-MMP-7, CLEC3B, Bax, HSP60, PARVB, HAI-1, FoxO1, SOD1, APCS, Desmoglein-2, ProSAAS, ALDH9A1, EphA4, C4.4A, Corneodesmosin, MICB, HPD, CAD, HSPA8, RPS20, Serpin A7, TNK1, IDUA, SHP-1, FGF-11, Serpin A11, TWF2, SSEA-1, Proteasome subunit beta type 2/PSB2, FLG2, MIP-1d, p53, Kallikrein 6, SHBG, Hemopexin, GRP, PTN, DEFA6, Talin1, NASP, MIP 2, EIF3S2, VCP, Chem R23, Ceruloplasmin, TFF3, HN1, ITIH2, APJ, HPRT, RYK, EN2, ETL, TRKB, GM2A, KRT82, ERp29, MMP-13, ATPB, Cardiotrophin-1/CT-1, CBP, ZC3H8, Presenilin 2, CALML5, Cystatin B, AR (Amphiregulin), Presenilin 1, SART3, S100A7, Laminin gamma 1, LPS, MANF, ASH2L, GLRX1, NRG3, LH, ENSA, FRY, DDX3Y, GNB1, Proteasome 20S alpha 5, NF1, Proteasome 26S S5, TRPM7, Oxytocin-neurophysin 1/OXT, C1RL, Thymosin b10, BPIFB1, VIP Receptor 2, MFAP4, Fibrillin 1, Desmin, PAK7, CD27/TNFRSF7, Integrin alpha V, HRSP12, 14-3-3 zeta, SAA4a, Syndecan-3, Cezanne, PEPSINOGEN I, PPARg2, LTBP4, GATM-C-terminal, IL-17D, IL-12 p40, TPA, SOD-3, Serpin B6, Legumain, OBCAM, MCP-2, CA 19-9, IL-10 R beta, Procalcitonin, Thrombin, IL-1 F7/FIL1 zeta, EHD3, Gelsolin, Calbindin D, FCGBP, CHORDCI, gamma Catenin, BACE-1, Calreticulin, EphA8, Granzyme M, Thrombospondin-2, Wilms Tumor 1, FOXN3, SPEN, VDUP-1, POMC, Tyk2, C6-N-t, PDE1B, TAB182, IL-16, Rbm15, Cytokeratin 19, SOD2, Eosinophil derived neurotoxin/EDN, Pro-MMP-9, Lubricin, GMNN, 67LR, TRPS1, Dopamine beta Hydroxylase/DBH, ITGB4BP, hnRNP U, IDH1, SynCAM, KIAA 1967, CEA, Resistin, Syntaxin 7, NET1, CS, COL19A1, EphB1, EPPK1, C9orf40, LOX, Lymphotoxin beta R/TNFRSF3, Neuropeptide Y, p39, DDT, MCMP2, GNPTG, Angiopoietin-like 2, C1P29, TOP2B, Corticosteroid-binding globulin, non-muscle Myosin IIA/Myosin, BAFF, C2, Plxdc2, FUCA2, Ube2L3, DMRN9, CARHSP1, GDF9, SMAC, MAGP-2, CYTL1, GARNL1, EMSY, BMPR-IB/ALK-6, PCNA, Apex1, LAMP1, Filamin A, pro-Glucagon, VEGF R1, Beta 2M, IL-10 R alpha, ROS, HE4, ZDHHC18, ALK, CLPS, RPL17, Proteasome subunit beta type 4/PSB4, Ubiquitin, LCMT2, Versican isoform V0, hnRNP A2B1, Envoplakin, GPCR GPRI 16, LTK, Vasopressin, Vitamin D Receptor, SDF4, TRPC1, CA150, COTL1, HMGN2, NAPRT1, hGH, SMA, Glutamyl hydrolase gamma/CGH, CCL14/HCC-1/HCC-3, GRHPR, Prosaposin, COLEC10, TROPONIN I, MDH2, PSP, Ghrelin, MTUS1, Netrin G2, ALS, Notch-2 ICD, FBP 38, FAK, Intergrin a6, DAN, BLC/BCA-1/CXCL13, Troponin C, PF4V1, G3BP, ADAMDEC1, CCDC126, ACACA, EphA5, Hck, NRG2, hnRNP C1+C2, MYL3, Peroxiredoxin 5, Vitamin K-dependent protein S, PTK 7, UQCRH, SYK, CART, Serpin A4, TXNDC4, Apo (a), APM2, ITGB5, 14-3-3 gamma, Dermcidin, AKR7A2, ORP150, VWF, Cytokeratin 4, GPI, CCDC25, MIP-1b, Midkine, DSPG3, AKAP9, BAD, Apolipoprotein L 2, LMW-PTP/ACP1, EFEMP2, HTRA2, Kallikrein 8, KLF4, EMILIN1, XEDAR, Aconitase 1, CHI3L1, hCGb, DARS2, UPB1, ERp72, HIP1R, BD-1, Ctip2, D4 GDI, CCK, PCPE-1, CRP, Cux2, MAG12, MyBPC3, ARP2/3, EEF2, Kallikrein 2, Tryptophanyl, LTA4H, PGAM1, PSMA2, alpha 1,2 Mannosidase IA/MAN1A1, Cytokeratin 16, SRMS, GDA, C3orf75, FASTKD5, CETP, DPP3, ARFGEF3, Calpain 1, Csk, Cytokeratin 15, DEFA1/3, Nucleobindin 1/NUCB1, Factor XII, ENO1, BRSK1, fast skeletal Myosin, Factor V, ASXL1, mGLUR5, Cytokeratin 10, ESR1, beta III Tubulin/CUBB3, LDHB, TRPC6, Serotonin, p23, CPA1, Ahsp, Kilon, Protein Z, Calpastatin, BIN2, EphB3, MFI2, Cytokeratin 3, EPHX2, Cytokeratin 5, PCAF, ASK1, CLTA, CNDP1, MPCA, Mimecan, HSC70, Fumarylacetoacetate hydrolase/FAH, GHRF, ADH1B, ITIH1, DNER, MBP, Apelin, LYPA1, CACNB4, BPGM, Cadherin 22, HIBADH, VGF, ABAT, G0/G1switch 2, Ephrin B2, SCG3, ERAB, CHREBP, Hemoglobin subunit delta/HBD, C1qTNF1, Haptoglobin, D-Dimer, Calmodulin, EphA7, alpha Tubulin, PRSS23, Cytokeratin 20, Tec, Coronin 3, TIM-4, CD 163, MGP, Aspartate Aminotransferase/AST, MYH6, Karyopherin beta 1, DR3/TNFRSF25, CECR1, ACTBL2, CNN2, BMPR-TA/ALK-3, BMP-4, GDI1, TYRO10, TAF4, hnRNP M1-M4, ZAP70, Stathmin 1, HLA-C, Argininosuccinate Lyase/ASL, Integrin beta 6, TRF 2, Chromogranin C, CLEC14A, ENPP2, Itk, MCM, Bcl-w, PI 3Kinase p85 beta, PTPRD, LEKTI/SPINK5, Lyn, Fen 1, Factor IX, CRMP2, EPB41, MINA, PCBP1, Lck, KHSRP, DAK, IL-1 R4/ST2, Histone H2A.Z, ESD, CO4A2, ZAG, C8G, HABP2, Histone H1.2, ACAA2, Cytokeratin 13, Bassoon, Alpha 1 Microglobulin, COL9A3, BAF57, PTH, ART3, ADAMTS-4, EEF1G, Androgen Receptor, MATK, KCC3, Eps 15, Non-muscle Actin/Actin, Chromogranin A, GST, FBP2, BID, MMP-19, MDH1, Selenoprotein P, Arp2, KMT2B, CPS1, Calretinin, Apolipoprotein F, ACAA1, HSP27, CEP57, IGFBP-1, PCMT1, BPIL1, eIF4A1-N-t, Alpha Lactalbumin, PDGF R alpha, CENPF, Creatine Kinase MM/CKMM, Asialoglycoprotein Receptor 2/ASGR2, Phosphoserine Aminotransferase/PSAT1, Gastrin, Aldolase C, CAPZA1, IDH3A, Keratin 38, GOT2, Alpha Fodrin, GLUD1, D6, GBE1, Krt73, E1 Ubiquitin Activating Enzyme/UBA1, BCOR, CPN1, PTEN, Cathelicidin, GPLD1, MCM5, NQO2, GCDFP 15, RET, A1BG, HEXA, Acetyl-CoA acetyltransferase/ACAA, Glucosidase 2 subunit beta/PRKCSH, KRT72, KIF5B, PPP2RIB, gamma-Thrombin, Alcohol Dehydrogenase/ADH, EHD1, COPS8, FRK, IGF2BP2, alpha Glucosidase II, KSR1, CPN2, LAG-3, AK2, PEPD, ADAS, Creatinine, COL4A3, LMAN2, RIP1, Cytokeratin 9, SPARCL1, Filamin C, MIP-3 beta, KRT85-N-terminal, LAD, GOLPH4, Cytoehrome b5, ADH4, ARPC2, LYRIC, Angiopoietin-1, FDPS, Apolipoprotein L 1, DPEP2, Vitamin D-BP, Ankrd26, APA, ArgRS, Fibrinopeptide B, LAP3, Ihh, ALDH16A1, IQGAPI, LASP1, Integrin b1, DPPI, TRAP220, Glutathione Synthetase/GSS, BASP1, Btk, ATPSA, Keratin 36, ECHS1, Desmocollin 1, DRIL1, LTF, GART, Contactin-3, S100 A8/A9, Arp3, GOLPH2, ISOC2, alpha Actinin 4, GREMLIN, Frizzled 8, LAM b1, PTHLP, LAF4, and/or MMP-20.

In various aspects, at least one component isolated from the extracellular matrix (an “ECM component”) may be present in the exosome composition at a concentration at least at least 5 times, 10 times, at least 20 times, at least 30 times, at least 40 times, or at least 50 times the concentration of the ECM component in a comparable exosome preparation, as defined below.

In various aspects, the exosome composition may comprise at least one ECM component at a concentration at least 5 times the concentration of the ECM component in a comparable exosome preparation (e.g., one prepared using ultra-centrifugation). For example, the exosome composition may comprise one or more of the following ECM components at a concentration that is at least 5 times the concentration of the ECM component in a comparative exosome preparation (e.g., prepared using ultra-centrifugation): Cysteine-rich Protein 1, PIM2, Cadherin-13, Beta IG-H3, EG-VEGF/PK1, Cyclophilin A, Dkk-3, BMP-3, QDPR, PAM, EDAR, EGF R/ErbB1, ALCAM, CXCR3, SBP-1, BCMA/TNFRSF17, CCL28/VIC, IL-29, HSP47, VE-Cadherin, I-309, TGF-beta RIII, CCR8, Fractalkine, TCN1, RSU1, uPAR, VEGF-D, PRELP, TGF-beta RII, Thrombopoietin (TPO), Endothelin, S100A6, Angiogenin, TIMP-4, MSP alpha Chain, Activin A, DMGDH, Serpin B8, TRAIL R3/TNFRSF10C, CFHR5, Caspase-14, PRDX 1, FGF-12, CXCR5/BLR-1, Semaphorin 7A, SPINK7, NT-4, TNF RII/TNFRSF1B, 6Ckine, SerRS, Angiostatin, Angiopoietin-like Factor, B7-1/CD80, Protein C, Tcf20, TROY/TNFRSF19, EMAP-II, CSH1, TLR4, RPLP0, ErbB3, RPL11, PGK-1, FGF-16, Plakophilin 1, PRCP, RAGE, Insulin, TSR2, NT-3, USP14, VDAC1/Porin, Proteasome 20S a+b, M-CSF, IL-2, ICAM-1, NEDD8, PRG2, Insulysin/IDE, ICAM-2, MMP-1, Salivary alpha amylase/aAmylase, IL-17F, Galectin-1, Lymphotoxin beta/TNFSF3, TBCA, PREP, VAP-A, Utrophin, YB1, VAP-1, CFHR4, FGF-20, Cyclophilin B, RNASE4, SBSN, FGF R4, FGF-17, PGLS-C-t, Eotaxin-3/CCL26, RREB1, TMEM223, ADAMTS-15, Semenogelin II/SEMG2, C3a, RPL12, GDF8, IGF-II, RPS25, Follistatin-like 1, Smad 5, Notch-2, I-TAC/CXCL11, TRANCE, MMP-3, uPA, WDR1, UQCRB, DR6/TNFRSF21, BMP-15, PSMA4, ErbB4, Gephyrin, beta-NGF, BMP-2, BMP-6, NAP-2, LECT2, FGF-13 1B, Reg3A, CD14, SHIP, RPL5, VEGF, IL-1 F5/FIL1delta, RPS28, TUBA6, Endostatin, MMP-9, CK-MB, CapG, IL-11, Ribonuclease A, Eotaxin-2/MPIF-2, GLO-1, TLR3, HGF, Sterol carrier protein 2/SCP2, Visfatin, SHC1, IL-18 R beta/AcPL, SIGLEC14, PRTN3, Contactin-1, CV-2/Crossveinless-2, EDG-1, CXCL14/BRAK, TIMP-3, Serpin A 1, Annexin A1, TGM3, CXCR6, PGM1, Osteoprotegerin/TNFRSF11B, Coagulation Factor III/Tissue Factor, M-CSF R, MDC, FAM3B, MMP-11/Stromelysin-3, SCF R/CD117, TGF-beta 5, Titin, sFRP-3, IL-1 beta, HCC-4/CCL16, TRAIL/TNFSF10, Fascin, BNP, ADAMTS-13, PLOD1, FLRG, LDHA, LIF, YY1, NME3, ESAM, RPS19, EpCAM, TAGLN2, CXCL16, BTF3, Hemoglobin subunit beta/HBB, TRADD, Metavinculin, BDNF, Galectin-7, PPP2R4, FACX, PDZD2, IL-26, FGF-9, Fibrinogen-like 2, Plexin B2, Thrombomodulin, Dtk, TRAIL R2/DR5/TNFRSF10B, PNP, ANGPTL8, B7-H3, ACLP, Galectin-3, p73, IL-4, IL-13 R alpha 2, TOB2, Claudin-3, IL-8, VEGF-C, IGF-I SR, Tenascin X(1), Lefty-A, Thrombospondin-1, OSM R beta, SUCLG1, PDGF-AB, IL-6 R, IL-18 BPa, PGAM2, Cripto-1, FGF-23, GSTM1, ICAM-5, RPL10, Ribonuclease Inhibitor, ARTS1, Periostin, UCH-L1, Zyxin, RPLI0A, PDLIM5, IL-15 R alpha, FAM3C, Tropomyosin 3, LZTS1, LIGHT/TNFSF14, Osteoadherin(2), SHMT1, CCR9, TWEAK R/TNFRSF12, TPP1, ADAMTS-10, RCL, PCDH7, MIG, SPARC, SH3BGRL, Thrombospondin-4, UFM 1, Prostaglandin D Synthase/PTGDS, GPR-39, SPTBN1, BLVRB, RKIP, 4-1BB, Decorin, CRIM 1, PCSK9, STil, IL-22 BP, VEGF R2 (KDR), Ficolin-2, CXCR4 (fusin), SIGIRR, IFN-beta, Cyclin D1, MIP-1a, RPS11, Alpha 1 AG, BLAME, Cystatin E/M, GM-CSF R alpha, Uteroglobin(1), Trypsinogeb-2, MCP-3, Erythropoietin R, Proteasome subunit alpha type 6/PSMA6, TGF-alpha, Flt-3 Ligand, Nanog, TNF-alpha, Spectrin beta-5, VNN1, BMP-1, FGF-7/KGF, OSM, FGF R5, Transferrin, C5/C5a, ApoA1, TCP1 eta, Galectin-3BP, PTPRZ, TRAIL R1/DR4/TNFRSF10A, Six3, SORD, CNTF, GDNF, BMPR-II, CXCR2/IL-8 RB, FGF-8, RPS5, CRF21, PGDF/PHGDH, FABP1, SLURP1, CEACAM-8/CD66b, UNC45A, Adiponectin/Acrp30, MMP-25/MT6-MMP, SMC4, Ornithine Carbamoyltransferase/OTC, IFN-gamma RI, CCR4, Proteasome beta 1, Talin1&2, Prohibitin, MMP-24/MT5-MMP, SP-D, Nidogen-2, PTPRS, SIRP beta 1/CD172b, APRIL, ACE-2, IL-6, HGFA, E-Selectin, GATA-4, VEGF R3, UBE2D3, BAFF R/TNFRSF13C, Layilin, Cytokeratin 8, Profilin 1, Cathepsin B, Marapsin, Lymphotactin/XCL1, Nidgen-1, MEP1A, MIF, IL-1 F8/FIL1 eta, MMP-14, HB-EGF, Latent TGF-beta bp1, C8B, SMPD4, ADAMTS-18, FGF Basic, IL-12 R beta 2, MINPP1, URP2, Glycoprotein V, LRG1, ACPP, AlphaA Crystallin/CRYAA, EDA-A2, SH3BGRL3, Serpin F2, CD40 Ligand/TNFSF5/CD154, CPEB3, A2M, Activin B, SREC-II, EGF, FGF-19, Myoferlin, Endoglin/CD105, RECK, ADAM-9, SSEA-4, DDAH1, P-Cadherin, IL-22 R, Glut1, Symplekin, S100A11, SLITRK1, GCP-2/CXCL6, SDPR, IGF-II R, P4HB, TNF-beta, IL-1 R8, IL-1 alpha, Angiopoietin-4, TCCR/WSX-1, GITR/TNFRF18, ILK, TCEB2, RPL22, DEP-1, FGF-18, TLIA/TNFSF15, EphA6, IL-36RN, Tarc, UROC1, Activin C, FASN, PYGL, Somatostatin, Musk, PLA2G1B, IL-1 R3/IL-1 R AcP, FGF-6, IL-18 R alpha/IL-1 R5, Tie-2, NIT2, PF4/CXCL4, TPM1, GDF11, IGFBP-6, Thymopoietin, FUCA1, CRHBP, C1qR1, STAT3, TPM4, Follistatin, Laminin b2, IL-1 sR1, CCR7, ApoA2, ENA-78, Myosin 18B, Desmoplakin, Neurabin 1, FGF-4, PDGF-BB, PCBP2, P20Sb3, IGF2BP1, Chordin-Like 2, UNC-13 Homolog D, Enolase 2, Angiopoietin-2, TFF2(1), RHOC, SUMO3, DGK, HVEM/TNFRSF14, GRO-a, GALNT2, TECK/CCL25, Notch-1, Cystatin S, IL-2 R alpha, WNK2, eIFSA, TrypsinPan, SCF, CD30/TNFRSF8, IL-1 F6/FIL1 epsilon, CutA, CFL1, TRAIL R4/TNFRSF10D, MBD2, UBE2N/Ubc13, PI 16, DANCE, FABP2, IGFBP-4, NEP, NRG1 Isoform GGF2, IL-2 R gamma, MAC-1, MPO, SerpinE2, GDF1, IL-17, Orexin A, Kremen-1, Smad 4, IL-17B R, GCSF, Annexin V, IL-31, TRAP1, Transketolase/TALDO, pTgR, Brg1, BMX, MAN1, Orosomucoid 2, RAP1AB, VEGF-B, SLC38A10, RPS2, RANTES, SerpinB4, Nestin, Complement factor H, MAPRE1, PDGF-AA, Reg1A, MUCDHL, SSTR2, IGSF4B, TSG-6, Orexin B, Quiescin Q6, IGFBP-2, IGFBP-rp1/IGFBP-7, Dystroglycan, Alanine Transaminase/ALT, FKBP12, Growth Hormone R (GHR), MCP-1, IL-21, RANK/TNFRSF11A, HRG-beta 1, ACTC1, Ribonuclease T2, B3GNT1, Src(1), PCYOX1, Leptin R, IL-19, CXCR1/IL-8 RA, PTP mu, IL-1 ra, PDGF-D, HEXB, ERp57, PLC-gamma 1, Nesprin2, Frizzled-4, B7-H2, NAGLU, Serpin B5, TNF RI/TNFRSF1A, IL-1 F9/IL-1 H1, Histone H2B K, OX40 Ligand/TNFSF4, Aminoacylase, Transaldolase 1/TALDO1, Glucagon, IFRD1, sFRP-4, IL-22, Kininostatin/kininogen, PRDM13, CCR5, C 1q, AMPKa1, EXTL2, POR, Smad 8, TXNDC5, IL-17RD, TREM-1, SDNSF, FKBP51, Complement Factor B, Cadherin-6, VCAM-1 (CD106), 11b-HSD1, Tie-1, Vimentin B, DISC 1, RPL7A, GDF-15, IL-31 RA, IL-5 R alpha, p16 ARC, EN-RAGE, Biglycan, DSCAM, Aggrecan, DCI, Cathepsin A, HGFR, sFRP-1, IL-4 R, IL-5, FGF R3, Activin RIA/ALK-2, Prdx6, Cathepsin L, Ezrin, TAX1BP3, FGF-BP, AMICA, KMD4B, Artemin, Axl, Claudin-4, SDF-1/CXCL12, FADD, MAPiA, ABCF1, Annexin A6, G-CSF R/CD 114, TSLP R, BRCA 2, EphA2, Cystatin SN, Fas Ligand, Pappalysin-1, ME1, 2B4, Fc RIIB/C, Dkk-4, alpha-Synuclein, Neural Cadherin, ANGPTL3, C1q S, ATBF1/ZFHX3, IGF-I, IL-3, IL-3 R alpha, Semaphorin 6B, DPPIV, LAMP2, Angiopoietin-like 1, ERAP2, PCDX8, ALKP, TMEFF2, IFN-alpha/beta R2, STOM, HSP20, Ck beta 8-1, IL-2 R beta/CD122, NrCAM, MMRN1, OSCAR, IL-21 R, PTMA, BLMH, PLS3, IL-10, CPM, cIAP-2, Pref-1, GASP-1/WFIKKNRP, FAP, Fibrinogen, PPCS, LFA-1 alpha, Mcl-1, DcR3/TNFRSF6B, Mesothelin, TACI/TNFRSF13B, Chemerin, WISP2, GM-CSF, DLL4, TLS/FUS, AGA, BTC, Chromogranin B, HMGB3, CFVII, Cryptic, CCR6, CrkL, 14-3-3 beta, TGF-beta RI/ALK-5, EphA1, Trypsin 1, Lipocalin-1, Podocalyxin, sgp130, Lipocalin-2, Caspase-3, ITIH4 a, FSH, Ras, PTP kappa, TIMP-1, Calsyntenin-1, MARCKS, ARP19, Fibronectin, Activin RIB/ALK-4, Chitobiase, OSBP1, IL-23, IL-12 R beta 1, GCSH, PLOD2, Nectin-3, GRP75, Soggy-1, MIP-3 alpha, GFR alpha-4, HMGB1, PCK2, LRP-1, MMP-8, HSP70, EPCR, Epiregulin, Gasl, CTLA-4/CD152, IL-27, TGF-beta 1, Attractin, BNIP2, BMP-5, PKLR, CCR3, Histone H2A, PDGF-C, IL-17B, Osteoactivin/GPNMB, CPE, CD40/TNFRSF5, CA1, Triosephosphate isomerase/TPIS, ADAMTS-17, EYA2, GFR alpha-1, Amylin, DMP-1, NUP98, SERPING1, CKB, CCR2, pro-MMP13, ApoC1, Glucose 6 Phosphate Dehydrogenase/G6PD, Caldesmon/CALD1, TLR2, NGF R, PSA-Free, COCO, MRP 1, MCAM, GRP78, IL-9, IL-1 R9, NAIP, RBP4, PABP, CEACAM-1, ADAMTS-5, ALPP, GPX1, Cathepsin X/Z/P, ApoB, Contactin-2, LRP-6, MMP-2, MFRP, Survivin, Siglec-1, PD-ECGF, cTnT, Thioredoxin-1, PGD, RPS23, TPX, LAMP, Myotrophin, SSTR5, IP-10, PGRPL, GDF7, FAM20C, ARFBP1, Activin RIIA, Sonic Hedgehog (Shh N-terminal), ApoC2, CFI, Adipsin, C7, ApoM, HRG, Fibulin 3, HINT1, GPBB, GDF5, Histone H1.3, RELM beta, glutathione S transferase Omega 1/GSTO1, Serpin A3, ErbB2, XIAP, IBSP, MICA, Desmocollin-3, Prolactin, Leptin (OB), WISP-1/CCN4, Aldolase B, NPAS3, LOX-1, hnRNP G, PACS1, BIK, Glycerol 3 Phosphate Dehydrogenase, Olfactomedin-2, GFR alpha-2, MSH6, ANGPTL4, Prouroguanylin, PHAP1, FKBP25, BMP-8, CFHR 1, Osteocalcin, HBZ, HOXD11, LEDGF, NeuroD1, RanGAP1, NF-M, SOX17, PYY, IL-20, Cytochrome c, IL-15, CA 15-3, Hemoglobin, DCBLD2, Serpin II, DLL1, FGF-21, RNASE6, Annexin A7, PCCA, GLIPR2, Desmuslin, C9, Proteasome 20S b7, ARX, LIF R alpha, C1s, Chymase, Prion protein PrP/PRNP, IFN-gamma, CNOT1, UROD, IL-1 R6/IL-1 Rrp2, PER1, CFHR2, Thymidine Kinase-1, PTP gamma, LBP, BCAM, NM23-H1/H2, Lysozyme, Frizzled-5, PARC/CCL18, ROR1, Serpin A8, Persephin, IL-13 R alpha 1, IGFBP-3, Neurturin, perilipin 3, PSMB5, PLUNC, Cathepsin G, Siglec-9, MMP-15, Frizzled-7, ARB1, CL-P1, Glypican 3, MFG-E8, GATA-3, Frizzled-6, beta B1 Crystallin/CRYBB1, Siglec-5/CD170, TOPORS, PIN, Hemoglobin A1c, S100A8, EphB4, CLC, Cystatin A, Transthyretin, GSR, GAPDH, Trappin-2, Plastin L, PSMA1, Cathepsin S, IGFBP-5, LILRA3, GITR Ligand/TNFSF18, KRT31, KCTD10, BTD, LYVE-1, ACE, ECM-1, ZNF671, FoxP3, ROBO4, Cystatin C, BIRC6, Vitronectin, beta-Catenin, beta-I Tubulin, E-Cadherin, IL-1 sRII, Plectin, Spinesin, Endorepellin, Glut2, Insulin R, Serpin D1, Azurocidin, RPS10, Catalase, Glut5, HAI-2, FGFR 1 alpha, S100A4, ARPC3, Properdin, Glyoxalase II, Netrin-4, FABP3, ZBTB4, LIMPII, Neuritin, BMP-3b/GDF-10, Vasorin, Cortactin, Cystatin D, Smad 1, MCP-4/CCL13, Syndecan-1, Osteopontin, ApoE, APN, IFN-alpha/beta R1, Fas/TNFRSF6, Erythropoietin, ApoB100, Cathepsin H, TWEAK/TNFSF12, Chordin-Like 1, Pentraxin3/TSG-14, AFP, CD61, Cathepsin D, DOTIL, Desmocollin-2, URB, PRSS3, MASP3, ADAMTS-19, Ephrin B1, TGF-beta 3, ApoH, ALDH1A1, Nectin-1, GFAP, KLK-B1, Secretogranin V/SCG5, Peroxiredoxin 3, EphB6, MYHC, NABC1, PSMD1, AgRP, IL-23 R, Galanin, PIK3IP1, IL-1 F10/IL-1HY2, IL-28A, SOX4, ANK, PON1, Uromodulin, PPOX, Histone H4, Metallothionein, FOLR3, Neurokinin-A, Protein p65, IL-33, HDGF, APLP-1, Frizzled-3, PGRP-S, SOD4, SERPINB1, Tenascin C, GMF beta, Fyn, HPR, Neuropilin-2, Lamin A+C, ZC3H4-N-t, GSTP1, PON2, DCXR, GRO, Hornerin, COX-2, S100A10, 53BP1, PKM2, S-100b, Lamin B1, PZP, Chitotriosidase, Osteocrin, PlGF, LOK, ALBUMIN, SHANK1, TLR1, HADHA, ApoD, PA2G4, KIF3B, Ubiquitin+1, TXNRD2, Eotaxin/CCL11, HCFC1, IL-20 R beta, Pancreastatin, FGF-10/KGF-2, Brevican, CES1, TIMP-2, MMP-10, CD30 Ligand/TNFSF8, GIP, Kallikrein 10, Ficolin-3, HNF-3 alpha/FoxA1, Thyroglobulin, TFPI, ICAM-3 (CD50), RPL14, S100A9, CA2, Hoxb3, Serpin A9, IL-20 R alpha, TFF1, Pro-BDNF, NCAM2, NPTXR, Guanylin, ALP, TMEFF1/Tomoregulin-1, PSA-total, KIAA1468, IL-7 R alpha, HSP10, GASP-2/WFIKKN, SLPI, Neogenin, Cerberus 1, PSMA7, Beta Defensin 4, FIH, CHC17, Semenogelin 1/SEMG1, hHR23b, Proteasome 20S alpha, Histone H3.3, SOST, EV15L, Fetuin A, Fetuin B, GULPI/CED-6, WIF-1, GDF3, INSL3, APC, TSLP, ROCK1, TRA-1-60, HOXA10, MYH7, ACLY, EVC2, CTGF/CCN2, TRA-1-81, 14-3-3 sigma, NELL2, Ferritin, Cytochrome C, B3GNT2, Fibrinopeptide A, PISD, SAMSN1, Glut3, HSP40, PD-1, PDGF R beta, SNCG, ROCK2, CRTH-2, MP1, CD200, PDIA6, Grb2, CNTF R alpha, F11, Frizzled-1, BMP-9, ROR2, L-Selectin (CD62L), Clusterin, AKRIC3, NCAM-1/CD56, S100P, COMP, FGFR1, PARK7, Laminin 2 alpha, PI 3-Kinase C2 beta, IRE1, Filamin B, NT5C3, Lumican, FGFR2, AIF, IL-34, Multimerin 2, Latent TGF beta bp2, ADM, Inhibin beta, FOLR1, SET, Progranulin, RELM alpha, Endothelin Receptor A, FABP4, PPP2R5C, ApoE3, MN1, RPS12, MLCK, INSRR, 14-3-3 epsilon, HP1BP3, Perilipin-1, Furin, ABL1, Mannosidase II, IL-17E, Grainyhead-like protein 1 homolog/GRHL1, Neurotrimin, CLIC1, LOXL1, 14-3-3 theta, RhoGDI, ACTH, Afamin, FBPase 1, Plasminogen, Kallikrein 11, Desmoglein-1, Myoglobin, Contactin-4, PECAM-1/CD31, ADH1C, ATP50, NOV/CCN3, CRTAM, Serpin B3/SCCA1, MBL, CA 125, Smad 7, Growth Hormone (GH), OX40, Serpin A5, TRP-1, PEPSINOGEN II, PEBP4, mTOR, hnRNP L, TACE, 14-3-3 eta, IL-17C, MMP-7, Kallikrein 7, AFG3L2, VEG1/TNFSF15, APP, LAIR1, Ran, Kallikrein 14, HSP90, Nesfatin, p27, TIM-1, Pancreatic Polypeptide, MYOSA, CPNE3, Peroxiredoxin 2, Nebulin, Aldehyde Oxidase 1/AOX1, BAZ2B, Actinin alpha 1, CA3, CCT3, MMR, Progesterone, HMGB2, PDX-1, Gastrokine 1, Factor XIII, TGF-beta 2, MMP-12, Caspase-8, PSMC3, ITM2B, PDLIM1, Plexin B1, H6PD, IL-12 p70, NAPIL1, NPM1, LRP 4, Prostasin, p21, SART1, SEZ6L2, VSIG4, SEMA3A, Hemoglobin subunit gamma 2/HBG2, IL-13, ANGPTL6, NR3C3, PEDF, Livin, ABI3BP, Noelin, HTRA1, FABP5, Kremen-2, SCGF, RPS3, B4GaIT1, ACK1, APOA1BP, ADAMTS-1, THOP1, IL-7, TSH, CLIP170-N-t, EphA3, IL-24, Ntnl, Fibrinogen gamma chain/FGG, Rab7a, SIM2, Neuropeptide B, HCR/CRAM-A/B, Serpin A12, OCT3/4, FER, ITIH3, LIN41, Mer, Hepassocin, PSMD9, hnRNP A1, BCHE, Omentin, SF20, IRS2, URB2, GPX3, MMP-16/MT3-MMP, GCLC, Cytokeratin 18, FH, IL-17RC, FGF-5, GFR alpha-3, GD12, Lamin B2, ELAVL1, UGGT, IL-17R, CTACK/CCL27, DBI, KRTDAP, SAA, MYH2, CRTAC1, HEG1, Annexin A2, P-selectin, PAI-1, Factor XIII B, Advillin-N-t, Destrin, LUZP1, Serpin A10/ZPI, HSP32, Kallikrein 5, OIT3, Dkk-1, KRTHA3B, ENO1+ENO2+ENO3, Endocan, MSHa, AKR1B1, TXK, Pro-Cathepsin B, SOX2, JAM-A, SERTAD2, BMP-7, SPINK1, CLIC4, Human Agrin, Aldolase A, UNC5H4, GLP-1, ERRa, EphB2, C5b-9, RNA Polymerase II/POLR2A, ASPH, ANP, Antithrombin III, Cytokeratin 14, PYK2, GRP, AHNAK, hCG alpha, SorLA, EFTUD2, Endorphin Beta, Cytokeratin 17, USP5, Granzyme A, CA 9, QPRT, JARID2, S100A1, ADAMTS-L2, Pleckstrin, RELT/TNFRSF19L, IBP160, nNOS, GADD45A, C-peptide, Moesin, Hepcidin, CCR1, Pro-MMP-7, CLEC3B, Bax, HSP60, PARVB, HAI-1, FoxO1, SOD1, APCS, Desmoglein-2, ProSAAS, ALDH9A1, EphA4, C4.4A, Corneodesmosin, MICB, HPD, CAD, HSPA8, RPS20, Serpin A7, TNK1, IDUA, SHP-1, FGF-11, Serpin A11, TWF2, SSEA-1, Proteasome subunit beta type 2/PSB2, FLG2, MIP-1d, p53, Kallikrein 6, SHBG, Hemopexin, GRP, PTN, DEFA6, Talin1, NASP, MIP 2, EIF3S2, VCP, Chem R23, Ceruloplasmin, TFF3, HN1, ITIH2, APJ, HPRT, RYK, EN2, ETL, TRKB, GM2A, KRT82, ERp29, MMP-13, ATPB, Cardiotrophin-1/CT-1, CBP, ZC3H8, Presenilin 2, CALML5, Cystatin B, AR (Amphiregulin), Presenilin 1, SART3, S100A7, Laminin gamma 1, LPS, MANF, ASH2L, GLRX1, NRG3, LH, ENSA, FRY, DDX3Y, GNB1, Proteasome 20S alpha 5, NF1, Proteasome 26S S5, TRPM7, Oxytocin-neurophysin 1/OXT, C1RL, Thymosin b10, BPIFB1, VIP Receptor 2, MFAP4, Fibrillin 1, Desmin, PAK7, CD27/TNFRSF7, Integrin alpha V, HRSP12, 14-3-3 zeta, SAA4a, Syndecan-3, Cezanne, PEPSINOGEN I, PPARg2, LTBP4, GATM-C-terminal, IL-17D, IL-12 p40, TPA, SOD-3, Serpin B6, Legumain, OBCAM, MCP-2, CA 19-9, IL-10 R beta, Procalcitonin, Thrombin, IL-1 F7/FIL1 zeta, EHD3, Gelsolin, Calbindin D, FCGBP, CHORDCI, gamma Catenin, BACE-1, Calreticulin, EphA8, Granzyme M, Thrombospondin-2, Wilms Tumor 1, FOXN3, SPEN, VDUP-1, POMC, Tyk2, C6-N-t, PDE1B, TAB182, IL-16, Rbm15, Cytokeratin 19, SOD2, Eosinophil derived neurotoxin/EDN, Pro-MMP-9, Lubricin, GMNN, 67LR, TRPS1, Dopamine beta Hydroxylase/DBH, ITGB4BP, hnRNP U, IDH1, SynCAM, KIAA1967, CEA, Resistin, Syntaxin 7, NET1, CS, COL19A1, EphB1, EPPK1, C9orf40, LOX, Lymphotoxin beta R/TNFRSF3, Neuropeptide Y, p39, DDT, MCMP2, GNPTG, Angiopoietin-like 2, CIP29, TOP2B, Corticosteroid-binding globulin, non-muscle Myosin IIA/Myosin, BAFF, C2, Plxdc2, FUCA2, Ube2L3, DMRN9, CARHSP1, GDF9, SMAC, MAGP-2, CYTL1, GARNL1, EMSY, BMPR-IB/ALK-6, PCNA, Apex1, LAMP1, Filamin A, pro-Glucagon, VEGF R1, Beta 2M, IL-10 R alpha, ROS, HE4, ZDHHC18, ALK, CLPS, RPL17, Proteasome subunit beta type 4/PSB4, Ubiquitin, LCMT2, Versican isoform V0, hnRNP A2B1, Envoplakin, GPCR GPR116, LTK, Vasopressin, Vitamin D Receptor, SDF4, TRPC1, CA150, COTL1, HMGN2, NAPRT1, hGH, SMA, Glutamyl hydrolase gamma/CGH, CCL14/HCC-1/HCC-3, GRHPR, Prosaposin, COLEC10, TROPONIN I, MDH2, PSP, Ghrelin, MTUS1, Netrin G2, ALS, Notch-2 ICD, FBP 38, FAK, Intergrin a6, DAN, BLC/BCA-1/CXCL13, Troponin C, PF4V1, G3BP, ADAMDEC1, CCDC126, ACACA, EphA5, Hck, NRG2, hnRNP C1+C2, MYL3, Peroxiredoxin 5, Vitamin K-dependent protein S, PTK 7, UQCRH, SYK, CART, Serpin A4, TXNDC4, Apo (a), APM2, ITGB5, 14-3-3 gamma, Dermcidin, AKR7A2, ORP150, VWF, Cytokeratin 4, GPI, CCDC25, MIP-Ib, Midkine, DSPG3, AKAP9, BAD, Apolipoprotein L 2, LMW-PTP/ACP1, EFEMP2, HTRA2, Kallikrein 8, KLF4, EMILIN1, XEDAR, Aconitase 1, CHI3L1, hCGb, DARS2, UPB1, ERp72, HIPIR, BD-1, Ctip2, D4 GDI, CCK, PCPE-1, CRP, Cux2, MAG12, MyBPC3, ARP2/3, EEF2, Kallikrein 2, Tryptophanyl, LTA4H, PGAM1, PSMA2, alpha 1,2 Mannosidase IA/MAN1A1, Cytokeratin 16, SRMS, GDA, C3orf75, FASTKD5, CETP, DPP3, ARFGEF3, Calpain 1, Csk, Cytokeratin 15, DEFA1/3, Nucleobindin 1/NUCB1, Factor XII, ENO1, BRSK1, fast skeletal Myosin, Factor V, ASXL1, mGLUR5, Cytokeratin 10, ESR 1, beta III Tubulin/CUBB3, LDHB, TRPC6, Serotonin, p23, CPA1, Ahsp, Kilon, Protein Z, Calpastatin, BIN2, EphB3, MFI2, Cytokeratin 3, EPHX2, Cytokeratin 5, PCAF, ASK1, CLTA, CNDP1, MPCA, Mimecan, HSC70, Fumarylacetoacetate hydrolase/FAH, GHRF, ADHIB, ITIH1, DNER, MBP, Apelin, LYPA1, and CACNB4.

In some aspects, the at least one ECM component is present at a concentration at least 5× and preferably at least 10× the concentration of the ECM component in a comparable exosome preparation (e.g., prepared via ultra-centrifugation). For example, the exosome composition may comprise one or more of the following ECM components at a concentration at least 20× that of a concentration of the ECM component in a comparable exosome preparation (e.g., prepared via ultra-centrifugation): Cysteine-rich Protein 1, PIM2, Cadherin-13, Beta IG-H3, EG-VEGF/PK1, Cyclophilin A, Dkk-3, BMP-3, QDPR, PAM, EDAR, EGF R/ErbB1, ALCAM, CXCR3, SBP-1, BCMA/TNFRSF17, CCL28/VIC, IL-29, HSP47, VE-Cadherin, I-309, TGF-beta RIII, CCR8, Fractalkine, TCN1, RSU1, uPAR, VEGF-D, PRELP, TGF-beta RII, Thrombopoietin (TPO), Endothelin, S100A6, Angiogenin, TIMP-4, MSP alpha Chain, Activin A, DMGDH, Serpin B8, TRAIL R3/TNFRSF10C, CFHR5, Caspase-14, PRDX 1, FGF-12, CXCR5/BLR-1, Semaphorin 7A, SPINK7, NT-4, TNF RII/TNFRSF1B, 6Ckine, SerRS, Angiostatin, Angiopoietin-like Factor, B7-1/CD80, Protein C, Tcf20, TROY/TNFRSF19, EMAP-II, CSH1, TLR4, RPLP0, ErbB3, RPL11, PGK-1, FGF-16, Plakophilin 1, PRCP, RAGE, Insulin, TSR2, NT-3, USP14, VDAC1/Porin, Proteasome 20S a+b, M-CSF, IL-2, ICAM-1, NEDD8, PRG2, Insulysin/IDE, ICAM-2, MMP-1, Salivary alpha amylase/aAmylase, IL-17F, Galectin-1, Lymphotoxin beta/TNFSF3, TBCA, PREP, VAP-A, Utrophin, YB1, VAP-1, CFHR4, FGF-20, Cyclophilin B, RNASE4, SBSN, FGF R4, FGF-17, PGLS-C-t, Eotaxin-3/CCL26, RREB1, TMEM223, ADAMTS-15, Semenogelin II/SEMG2, C3a, RPL12, GDF8, IGF-II, RPS25, Follistatin-like 1, Smad 5, Notch-2, 1-TAC/CXCL11, TRANCE, MMP-3, uPA, WDR1, UQCRB, DR6/TNFRSF21, BMP-15, PSMA4, ErbB4, Gephyrin, beta-NGF, BMP-2, BMP-6, NAP-2, LECT2, FGF-13 1B, Reg3A, CD14, SHIP, RPL5, VEGF, IL-1 F5/FIL1delta, RPS28, TUBA6, Endostatin, MMP-9, CK-MB, CapG, IL-11, Ribonuclease A, Eotaxin-2/MPIF-2, GLO-1, TLR3, HGF, Sterol carrier protein 2/SCP2, Visfatin, SHC1, IL-18 R beta/AcPL, SIGLEC14, PRTN3, Contactin-1, CV-2/Crossveinless-2, EDG-1, CXCL14/BRAK, TIMP-3, Serpin A1, Annexin A1, TGM3, CXCR6, PGM1, Osteoprotegerin/TNFRSF1 IB, Coagulation Factor III/Tissue Factor, M-CSF R, MDC, FAM3B, MMP-1 I/Stromelysin-3, SCF R/CD117, TGF-beta 5, Titin, sFRP-3, IL-1 beta, HCC-4/CCL16, TRAIL/TNFSF10, Fascin, BNP, ADAMTS-13, PLOD1, FLRG, LDHA, LIF, YY1, NME3, ESAM, RPS19, EpCAM, TAGLN2, CXCL16, BTF3, Hemoglobin subunit beta/HBB, TRADD, Metavinculin, BDNF, Galectin-7, PPP2R4, FACX, PDZD2, IL-26, FGF-9, Fibrinogen-like 2, Plexin B2, Thrombomodulin, Dtk, TRAIL R2/DR5/TNFRSF10B, PNP, ANGPTL8, B7-H3, ACLP, Galectin-3, p73, IL-4, IL-13 R alpha 2, TOB2, Claudin-3, IL-8, VEGF-C, IGF-I SR, Tenascin X(1), Lefty-A, Thrombospondin-1, OSM R beta, SUCLG1, PDGF-AB, IL-6 R, IL-18 BPa, PGAM2, Cripto-1, FGF-23, GSTM1, ICAM-5, RPL10, Ribonuclease Inhibitor, ARTS1, Periostin, UCH-L1, Zyxin, RPL10A, PDLIM5, IL-15 R alpha, FAM3C, Tropomyosin 3, LZTS1, LIGHT/TNFSF14, Osteoadherin(2), SHMT1, CCR9, TWEAK R/TNFRSF12, TPP1, ADAMTS-10, RCL, PCDH7, MIG, SPARC, SH3BGRL, Thrombospondin-4, UFM 1, Prostaglandin D Synthase/PTGDS, GPR-39, SPTBN1, BLVRB, RKIP, 4-1BB, Decorin, CRIM 1, PCSK9, STI1, IL-22 BP, VEGF R2 (KDR), Ficolin-2, CXCR4 (fusin), SIGIRR, IFN-beta, Cyclin D1, MIP-1a, RPS11, Alpha 1 AG, BLAME, Cystatin E/M, GM-CSF R alpha, Uteroglobin(1), Trypsinogeb-2, MCP-3, Erythropoietin R, Proteasome subunit alpha type 6/PSMA6, TGF-alpha, Flt-3 Ligand, Nanog, TNF-alpha, Spectrin beta-5, VNN1, BMP-1, FGF-7/KGF, OSM, FGF R5, Transferrin, C5/C5a, ApoA1, TCP1 eta, Galectin-3BP, PTPRZ, TRAIL R1/DR4/TNFRSF10A, Six3, SORD, CNTF, GDNF, BMPR-II, CXCR2/IL-8 RB, FGF-8, RPS5, CRF21, PGDF/PHGDH, FABP1, SLURP1, CEACAM-8/CD66b, UNC45A, Adiponectin/Acrp30, MMP-25/MT6-MMP, SMC4, Ornithine Carbamoyltransferase/OTC, IFN-gamma R1, CCR4, Proteasome beta 1, Talin1&2, Prohibitin, MMP-24/MT5-MMP, SP-D, Nidogen-2, PTPRS, SIRP beta 1/CD172b, APRIL, ACE-2, IL-6, HGFA, E-Selectin, GATA-4, VEGF R3, UBE2D3, BAFF R/TNFRSF13C, Layilin, Cytokeratin 8, Profilin 1, Cathepsin B, Marapsin, Lymphotactin/XCL1, Nidgen-1, MEP1A, MIF, IL-1 F8/FIL1 eta, MMP-14, HB-EGF, Latent TGF-beta bp1, C8B, SMPD4, ADAMTS-18, FGF Basic, IL-12 R beta 2, MINPP1, URP2, Glycoprotein V, LRG1, ACPP, AlphaA Crystallin/CRYAA, EDA-A2, SH3BGRL3, Serpin F2, CD40 Ligand/TNFSF5/CD154, CPEB3, A2M, Activin B, SREC-II, EGF, FGF-19, Myoferlin, Endoglin/CD105, RECK, ADAM-9, SSEA-4, DDAH1, P-Cadherin, IL-22 R, Glut1, Symplekin, S100A11, SLITRK1, GCP-2/CXCL6, SDPR, IGF-II R, P4HB, TNF-beta, IL-1 R8, IL-1 alpha, Angiopoietin-4, TCCR/WSX-1, GITR/TNFRF18, ILK, TCEB2, RPL22, DEP-1, FGF-18, TLIA/TNFSF15, EphA6, IL-36RN, Tarc, UROC1, Activin C, FASN, PYGL, Somatostatin, Musk, PLA2GIB, IL-1 R3/IL-1 R AcP, FGF-6, IL-18 R alpha/IL-1 R5, Tie-2, NIT2, PF4/CXCL4, TPM1, GDF11, IGFBP-6, Thymopoietin, FUCA1, CRHBP, C1qR1, STAT3, TPM4, Follistatin, Laminin b2, IL-1 sRI, CCR7, ApoA2, ENA-78, Myosin 18B, Desmoplakin, Neurabin 1, FGF-4, PDGF-BB, PCBP2, P20Sb3, IGF2BP1, Chordin-Like 2, UNC-13 Homolog D, Enolase 2, Angiopoietin-2, TFF2(1), RHOC, SUMO3, DGK, HVEM/TNFRSF14, GRO-a, GALNT2, TECK/CCL25, Notch-1, Cystatin S, IL-2 R alpha, WNK2, eiF5A, TrypsinPan, SCF, CD30/TNFRSF8, IL-1 F6/FIL1 epsilon, CutA, CFL1, TRAIL R4/TNFRSF10D, MBD2, UBE2N/Ubc13, P1 16, DANCE, FABP2, IGFBP-4, NEP, NRG1 Isoform GGF2, IL-2 R gamma, MAC-1, MPO, SerpinE2, GDF1, IL-17, Orexin A, Kremen-1, Smad 4, IL-17B R, GCSF, Annexin V, IL-31, TRAP1, Transketolase/TALDO, pIgR, Brg1, BMX, MAN1, Orosomucoid 2, RAPIAB, VEGF-B, SLC38A10, RPS2, RANTES, SerpinB4, Nestin, Complement factor H, MAPRE1, PDGF-AA, Reg1A, MUCDHL, SSTR2, IGSF4B, TSG-6, Orexin B, Quiescin Q6, IGFBP-2, IGFBP-rp1/IGFBP-7, Dystroglycan, Alanine Transaminase/ALT, FKBP12, Growth Hormone R (GHR), MCP-1, IL-21, RANK/TNFRSF11A, HRG-beta 1, ACTC1, Ribonuclease T2, B3GNT1, Src(1), PCYOX1, Leptin R, IL-19, CXCR1/IL-8 RA, PTP mu, IL-1 ra, PDGF-D, HEXB, ERp57, PLC-gamma 1, Nesprin2, Frizzled-4, B7-H2, NAGLU, Serpin B5, TNF RI/TNFRSF1A, IL-1 F9/IL-1 H1, Histone H2B K, OX40 Ligand/TNFSF4, Aminoacylase, Transaldolase 1/TALDO1, Glucagon, IFRD1, sFRP-4, IL-22, Kininostatin/kininogen, PRDM13, CCR5, C1q, AMPKa1, EXTL2, POR, Smad 8, TXNDC5, IL-17RD, TREM-1, SDNSF, FKBP51, Complement Factor B, Cadherin-6, VCAM-1 (CD106), 1 Ib-HSD1, Tie-1, Vimentin B, DISC 1, RPL7A, GDF-15, IL-31 RA, IL-5 R alpha, p16 ARC, EN-RAGE, Biglycan, DSCAM, Aggrecan, DCI, Cathepsin A, HGFR, sFRP-1, IL4 R, IL-5, FGF R3, Activin RIA/ALK-2, Prdx6, Cathepsin L, Ezrin, TAX1BP3, FGF-BP, AMICA, KMD4B, Artemin, Axl, Claudin-4, SDF-1/CXCL12, FADD, MAPIA, ABCF1, Annexin A6, G-CSF R/CD 114, TSLP R, BRCA 2, EphA2, Cystatin SN, Fas Ligand, Pappalysin-1, ME1, 2B4, Fc RIIB/C, Dkk-4, alpha-Synuclein, Neural Cadherin, ANGPTL3, C 1q S, ATBF1/ZFHX3, IGF-I, IL-3, IL-3 R alpha, Semaphorin 6B, DPPIV, LAMP2, Angiopoietin-like 1, ERAP2, PCDX8, ALKP, TMEFF2, IFN-alpha/beta R2, STOM, HSP20, Ck beta 8-1, IL-2 R beta/CD122, NrCAM, MMRN1, OSCAR, IL-21 R, PTMA, BLMH, PLS3, IL-10, CPM, cIAP-2, Pref-1, GASP-1/WFIKKNRP, FAP, Fibrinogen, PPCS, LFA-1 alpha, Mcl-1, DcR3/TNFRSF6B, Mesothelin, TACI/TNFRSF13B, Chemerin, WISP2, GM-CSF, DLL4, TLS/FUS, AGA, BTC, Chromogranin B, HMGB3, CFVII, Cryptic, CCR6, CrkL, 14-3-3 beta, TGF-beta RI/ALK-5, EphA1, Trypsin 1, Lipocalin-1, Podocalyxin, sgp130, Lipocalin-2, Caspase-3, ITIH4 a, FSH, Ras, PTP kappa, TIMP-1, Calsyntenin-1, MARCKS, ARP19, Fibronectin, Activin RIB/ALK-4, Chitobiase, OSBP1, IL-23, IL-12 R beta 1, GCSH, PLOD2, Nectin-3, GRP75, Soggy-1, MIP-3 alpha, GFR alpha-4, HMGB1, PCK2, LRP-1, MMP-8, HSP70, EPCR, Epiregulin, Gasl, CTLA-4/CD152, IL-27, TGF-beta 1, Attractin, BNIP2, BMP-5, PKLR, CCR3, Histone H2A, PDGF-C, IL-17B, Osteoactivin/GPNMB, CPE, CD40/TNFRSF5, CA1, Triosephosphate isomerase/TPIS, ADAMTS-17, EYA2, GFR alpha-1, Amylin, DMP-1, NUP98, SERPING1, CKB, CCR2, pro-MMP13, ApoC1, Glucose 6 Phosphate Dehydrogenase/G6PD, Caldesmon/CALD1, TLR2, NGF R, PSA-Free, COCO, MRP 1, MCAM, GRP78, IL-9, IL-1 R9, NAIP, RBP4, PABP, CEACAM-1, ADAMTS-5, ALPP, GPX1, Cathepsin X/Z/P, ApoB, Contactin-2, LRP-6, MMP-2, MFRP, Survivin, Siglec-1, PD-ECGF, cTnT, Thioredoxin-1, PGD, RPS23, TPX, LAMP, Myotrophin, SSTR5, IP-10, PGRPL, GDF7, FAM20C, ARFBP1, Activin RIIA, Sonic Hedgehog (Shh N-terminal), ApoC2, CFI, Adipsin, C7, ApoM, HRG, Fibulin 3, HINT1, GPBB, GDF5, Histone H1.3, RELM beta, glutathione S transferase Omega 1/GSTO1, Serpin A3, ErbB2, XIAP, IBSP, MICA, Desmocollin-3, Prolactin, Leptin (OB), WISP-1/CCN4, Aldolase B, NPAS3, LOX-1, hnRNP G, PACS1, BIK, Glycerol 3 Phosphate Dehydrogenase, Olfactomedin-2, GFR alpha-2, MSH6, ANGPTL4, Prouroguanylin, PHAP1, FKBP25, BMP-8, CFHR 1, Osteocalcin, HBZ, HOXD11, LEDGF, NeuroD1, RanGAP1, NF-M, SOX17, PYY, IL-20, Cytochrome c, IL-15, CA 15-3, Hemoglobin, DCBLD2, Serpin II, DLL1, FGF-21, RNASE6, Annexin A7, PCCA, GLIPR2, Desmuslin, C9, Proteasome 20S b7, ARX, LIF R alpha, Cis, Chymase, Prion protein PrP/PRNP, IFN-gamma, CNOT1, UROD, IL-1 R6/IL-1 Rrp2, PER1, CFHR2, Thymidine Kinase-1, PTP gamma, LBP, BCAM, NM23-H1/H2, Lysozyme, Frizzled-5, PARC/CCLI8, ROR1, Serpin A8, Persephin, IL-13 R alpha 1, IGFBP-3, Neurturin, perilipin 3, PSMB5, PLUNC, Cathepsin G, Siglec-9, MMP-15, Frizzled-7, ARB1, CL-P1, Glypican 3, MFG-E8, GATA-3, Frizzled-6, beta B1 Crystallin/CRYBB1, Siglec-5/CD170, TOPORS, PIN, Hemoglobin A1c, S100A8, EphB4, CLC, Cystatin A, Transthyretin, GSR, GAPDH, Trappin-2, Plastin L, PSMA1, Cathepsin S, IGFBP-5, LILRA3, GITR Ligand/TNFSF18, KRT31, KCTD10, BTD, LYVE-1, ACE, ECM-1, ZNF671, FoxP3, ROBO4, Cystatin C, BIRC6, Vitronectin, beta-Catenin, beta-I Tubulin, E-Cadherin, IL-1 sRII, Plectin, Spinesin, Endorepellin, Glut2, Insulin R, Serpin D1, Azurocidin, RPS10, Catalase, Glut5, HAI-2, FGFR1 alpha, S100A4, ARPC3, Properdin, Glyoxalase II, Netrin-4, FABP3, ZBTB4, LIMPII, Neuritin, BMP-3b/GDF-10, Vasorin, Cortactin, Cystatin D, Smad 1, MCP-4/CCL13, Syndecan-1, Osteopontin, ApoE, APN, IFN-alpha/beta R1, Fas/TNFRSF6, Erythropoietin, ApoB100, Cathepsin H, TWEAK/TNFSF12, Chordin-Like 1, Pentraxin3/TSG-14, AFP, CD61, Cathepsin D, DOTIL, Desmocollin-2, URB, PRSS3, MASP3, ADAMTS-19, Ephrin B1, TGF-beta 3, ApoH, ALDH1A1, Nectin-1, GFAP, KLK-B1, Secretogranin V/SCG5, Peroxiredoxin 3, EphB6, MYHC, NABC1, PSMD1, AgRP, IL-23 R, Galanin, PIK3IP1, IL-1 F10/IL-1HY2, IL-28A, SOX4, ANK, PON1, Uromodulin, PPOX, Histone H4, Metallothionein, FOLR3, Neurokinin-A, Protein p65, IL-33, HDGF, APLP-1, Frizzled-3, PGRP-S, SOD4, SERPINB1, Tenascin C, GMF beta, Fyn, HPR, Neuropilin-2, Lamin A+C, ZC3H4-N-t, GSTP1, PON2, DCXR, GRO, Hornerin, COX-2, S100A10, 53BP1, PKM2, S-100b, Lamin B1, PZP, Chitotriosidase, Osteocrin, PlGF, LOK, ALBUMIN, SHANK1, TLR1, HADHA, ApoD, PA2G4, KIF3B, Ubiquitin+1, TXNRD2, Eotaxin/CCL11, HCFC1, IL-20 R beta, Pancreastatin, FGF-10/KGF-2, Brevican, CES1, TIMP-2, MMP-10, CD30 Ligand/TNFSF8, GIP, Kallikrein 10, Ficolin-3, HNF-3 alpha/FoxA1, Thyroglobulin, TFPI, ICAM-3 (CD50), RPL14, S100A9, CA2, Hoxb3, Serpin A9, IL-20 R alpha, TFF1, Pro-BDNF, NCAM2, NPTXR, Guanylin, ALP, TMEFF1/Tomoregulin-1, PSA-total, KIAA1468, IL-7 R alpha, HSP10, GASP-2/WFIKKN, SLPI, Neogenin, Cerberus 1, PSMA7, Beta Defensin 4, FIH, CHC17, Semenogelin I/SEMG1, hHR23b, Proteasome 20S alpha, Histone H3.3, SOST, EVI5L, Fetuin A, Fetuin B, GULPI/CED-6, WIF-1, GDF3, INSL3, APC, TSLP, ROCK1, TRA-1-60, HOXA10, MYH7, ACLY, EVC2, CTGF/CCN2, TRA-1-81, 14-3-3 sigma, NELL2, Ferritin, Cytochrome C, B3GNT2, Fibrinopeptide A, PISD, SAMSN1, Glut3, HSP40, PD-1, PDGF R beta, SNCG, ROCK2, CRTH-2, MP1, CD200, PDIA6, Grb2, CNTF R alpha, F11, Frizzled-1, BMP-9, ROR2, L-Selectin (CD62L), Clusterin, AKRIC3, NCAM-1/CD56, S100P, COMP, FGFR1, PARK7, Laminin 2 alpha, PI 3-Kinase C2 beta, IRE1, Filamin B, NT5C3, Lumican, FGFR2, AIF, IL-34, Multimerin 2, Latent TGF beta bp2, ADM, Inhibin beta, FOLR1, SET, Progranulin, RELM alpha, Endothelin Receptor A, FABP4, PPP2R5C, ApoE3, MN1, RPS12, MLCK, INSRR, 14-3-3 epsilon, HP1BP3, Perilipin-1, Furin, ABL1, Mannosidase II, IL-17E, Grainyhead-like protein 1 homolog/GRHL1, Neurotrimin, CLIC1, LOXL1, 14-3-3 theta, RhoGDI, ACTH, Afamin, FBPase 1, Plasminogen, Kallikrein 11, Desmoglein-1, Myoglobin, Contactin-4, PECAM-1/CD31, ADHIC, ATP5O, and any combination thereof.

In still further aspects, the at least one ECM component is present at a concentration at least about 5 times, preferably at least about 20 times the concentration of the ECM component in a comparable exosome preparation (e.g., prepared via ultra-centrifugation). For example, the exosome composition may comprise one or more of the following components at a concentration at least 20× that of a concentration of the ECM component in a comparable exosome preparation (e.g., prepared via ultra-centrifugation): Cysteine-rich Protein 1, PIM2, Cadherin-13, Beta IG-H3, EG-VEGF/PK1, Cyclophilin A, Dkk-3, BMP-3, QDPR, PAM, EDAR, EGF R/ErbB1, ALCAM, CXCR3, SBP-1, BCMA/TNFRSF17, CCL28/VIC, IL-29, HSP47, VE-Cadherin, I-309, TGF-beta RIII, CCR8, Fractalkine, TCN1, RSU1, uPAR, VEGF-D, PRELP, TGF-beta RII, Thrombopoietin (TPO), Endothelin, S100A6, Angiogenin, TIMP-4, MSP alpha Chain, Activin A, DMGDH, Serpin B8, TRAIL R3/TNFRSF10C, CFHR5, Caspase-14, PRDX 1, FGF-12, CXCR5/BLR-1, Semaphorin 7A, SPINK7, NT-4, TNF RII/TNFRSF1B, 6Ckine, SerRS, Angiostatin, Angiopoietin-like Factor, B7-1/CD80, Protein C, Tct20, TROY/TNFRSF19, EMAP-II, CSH1, TLR4, RPLP0, ErbB3, RPL11, PGK-1, FGF-16, Plakophilin 1, PRCP, RAGE, Insulin, TSR2, NT-3, USP14, VDAC1/Porin, Proteasome 20S a+b, M-CSF, IL-2, ICAM-1, NEDD8, PRG2, Insulysin/IDE, ICAM-2, MMP-1, Salivary alpha amylase/aAmylase, IL-17F, Galectin-1, Lymphotoxin beta/TNFSF3, TBCA, PREP, VAP-A, Utrophin, YB1, VAP-1, CFHR4, FGF-20, Cyclophilin B, RNASE4, SBSN, FGF R4, FGF-17, PGLS-C-t, Eotaxin-3/CCL26, RREB1, TMEM223, ADAMTS-15, Semenogelin II/SEMG2, C3a, RPL12, GDF8, IGF-II, RPS25, Follistatin-like 1, Smad 5, Notch-2, I-TAC/CXCL11, TRANCE, MMP-3, uPA, WDR1, UQCRB, DR6/TNFRSF21, BMP-15, PSMA4, ErbB4, Gephyrin, beta-NGF, BMP-2, BMP-6, NAP-2, LECT2, FGF-13 1B, Reg3A, CD14, SHIP, RPL5, VEGF, IL-1 F5/FILidelta, RPS28, TUBA6, Endostatin, MMP-9, CK-MB, CapG, IL-11, Ribonuclease A, Eotaxin-2/MPIF-2, GLO-1, TLR3, HGF, Sterol carrier protein 2/SCP2, Visfatin, SHC1, IL-18 R beta/AcPL, SIGLEC14, PRTN3, Contactin-1, CV-2/Crossveinless-2, EDG-1, CXCL14/BRAK, TIMP-3, Serpin A1, Annexin A1, TGM3, CXCR6, PGM1, Osteoprotegerin/TNFRSF11B, Coagulation Factor III/Tissue Factor, M-CSF R, MDC, FAM3B, MMP-11/Stromelysin-3, SCF R/CD117, TGF-beta 5, Titin, sFRP-3, IL-1 beta, HCC-4/CCL16, TRAIL/TNFSF10, Fascin, BNP, ADAMTS-13, PLOD1, FLRG, LDHA, LIF, YY1, NME3, ESAM, RPS19, EpCAM, TAGLN2, CXCL16, BTF3, Hemoglobin subunit beta/HBB, TRADD, Metavinculin, BDNF, Galectin-7, PPP2R4, FACX, PDZD2, IL-26, FGF-9, Fibrinogen-like 2, Plexin B2, Thrombomodulin, Dtk, TRAIL R2/DR5/TNFRSF10B, PNP, ANGPTL8, B7-H3, ACLP, Galectin-3, p73, IL-4, IL-13 R alpha 2, TOB2, Claudin-3, IL-8, VEGF-C, IGF-I SR, Tenascin X(1), Lefty-A, Thrombospondin-1, OSM R beta, SUCLG1, PDGF-AB, IL-6 R, IL-18 BPa, PGAM2, Cripto-1, FGF-23, GSTM1, ICAM-5, RPL10, Ribonuclease Inhibitor, ARTS1, Periostin, UCH-L1, Zyxin, RPL10A, PDLIM5, IL-15 R alpha, FAM3C, Tropomyosin 3, LZTS1, LIGHT/TNFSFI4, Osteoadherin(2), SHMT1, CCR9, TWEAK R/TNFRSF12, TPP1, ADAMTS-10, RCL, PCDH7, MIG, SPARC, SH3BGRL, Thrombospondin-4, UFM 1, Prostaglandin D Synthase/PTGDS, GPR-39, SPTBN1, BLVRB, RKIP, 4-1BB, Decorin, CRIM 1, PCSK9, STI1, IL-22 BP, VEGF R2 (KDR), Ficolin-2, CXCR4 (fusin), SIGIRR, IFN-beta, Cyclin D1, MIP-1a, RPS11, Alpha 1 AG, BLAME, Cystatin E/M, GM-CSF R alpha, Uteroglobin(1), Trypsinogeb-2, MCP-3, Erythropoietin R, Proteasome subunit alpha type 6/PSMA6, TGF-alpha, Flt-3 Ligand, Nanog, TNF-alpha, Spectrin beta-5, VNN1, BMP-1, FGF-7/KGF, OSM, FGF R5, and Transferrin.

In still further aspects, the exosome composition may comprise ECM component at a concentration at least 5× and preferably at least 30× the concentration of the ECM component in a comparable exosome preparation (e.g., prepared via ultra-centrifugation). For example, the exosome composition may comprise one or more of the following ECM components at a concentration at least 30× the concentration of the ECM component in a comparable exosome preparation (e.g., prepared via ultra-centrifugation): Cysteine-rich Protein 1, PIM2, Cadherin-13, Beta IG-H3, EG-VEGF/PK1, Cyclophilin A, Dkk-3, BMP-3, QDPR, PAM, EDAR, EGF R/ErbB1, ALCAM, CXCR3, SBP-1, BCMA/TNFRSF17, CCL28/VIC, IL-29, HSP47, VE-Cadherin, I-309, TGF-beta RIII, CCR8, Fractalkine, TCN1, RSU1, uPAR, VEGF-D, PRELP, TGF-beta RII, Thrombopoietin (TPO), Endothelin, S100A6, Angiogenin, TIMP-4, MSP alpha Chain, Activin A, DMGDH, Serpin B8, TRAIL R3/TNFRSF10C, CFHR5, Caspase-14, PRDX 1, FGF-12, CXCR5/BLR-1, Semaphorin 7A, SPINK7, NT-4, TNF RII/TNFRSF1B, 6Ckine, SerRS, Angiostatin, Angiopoietin-like Factor, and B7-1/CD80.

In still further aspects, the exosome composition may comprise one or more ECM component at a concentration at least 5× and preferably at least 40× a concentration of the ECM component in a comparable exosome preparation (e.g., prepared via ultra-centrifugation). For example, the exosome composition may comprise one or more of the following ECM components at a concentration at least 40× the concentration of the ECM component in a comparable exosome preparation (e.g., prepared via ultra-centrifugation): Cysteine-rich Protein 1, PIM2, Cadherin-13, Beta IG-H3, EG-VEGF/PK1, Cyclophilin A, Dkk-3, BMP-3, QDPR, PAM, EDAR, EGF R/ErbB1, ALCAM, CXCR3, and SBP-1.

In still further aspects, the exosome composition may comprise one or more ECM component at a concentration at least 5× and preferably at least 50× a concentration of the ECM component in a comparable exosome preparation (e.g., prepared via ultra-centrifugation). For example, the exosome composition may comprise one or more of the following ECM components at a concentration at least 50× the concentration of the ECM compound in a comparable exosome preparation (e.g., prepared via ultra-centrifugation): Cysteine-rich Protein 1, PIM2, Cadherin-13, Beta IG-H3, EG-VEGF/PK1, and Cyclophilin A.

The concentration of any of the previous factors may be determined by one of skill in the art using standard techniques. For example, any of the factors listed above may be analyzed and quantified using standard proteomics (e.g., using mass spectrometry or other suitable analytical methods).

In any of the compositions provided herein, concentrations of one or more components may be compared to a “comparable exosome preparation”. As used herein a “comparable exosome preparation” refers to a purified exosome composition prepared using standard methods. Standard or traditional methods for purifying exosomes usually involves several centrifugation steps, each with increasing force. For example, one protocol to purify exosomes from a low viscosity mixture (e.g., urine or conditioned medium) is described in Dismuke et al., (“Current Methods to Purify and Characterize Exosomes” Mesenchymal Stem Cell Derived Exosomes: The Potential for Translational Medicine: Chapter 4. Edited by Yaoliang Tang and Buddhadeb Dawn. Academic Press. 2015) which is incorporated herein by reference in its entirety. As described, a multi-step process is followed where first a low-speed centrifugation step is applied to remove nonadherent cells, dead cells, and cellular debris followed by a high-speed centrifugation step to pellet exosomes. The initial exosomal pellet fraction may then undergo subsequent rounds of centrifugation to continue to purify the exosome composition. This sequential centrifugation process is also known as “ultra-centrifugation”. In contrast, the methods provided herein do not involve centrifugation. In certain aspects, the comparable exosome preparation may comprise a commercially available preparation (e.g., AMNIOSOMES as manufactured by Thrivell).

The exosome compositions provided herein may be provided in one or more unit dosages each comprising a concentration of exosomes that may be administered to a subject in order to treat a disease or disorder.

In various aspects, a unit dosage of the exosome composition may comprise about 500 million to about 500 billion exosomes. For example, the unit dosage may comprise about 500 million to about 5 billion exosomes, about 500 million to about 4.5 billion, about 500 million to about 4 billion, about 500 million to about 3.5 billion, about 500 million to about 3 billion, about 500 million to about 2.5 billion, about 500 million to about 2 billion, about 500 million to about 1.5 billion, about or about 500 million to about 1 billion. In other aspects, the unit dosage may comprise about 1 billion to about 5 billion, about 1 billion to about 4.5 billion, about 1 billion to about 4 billion, about 1 billion to about 3.5 billion, about 1 billion to about 3 billion, about 1 billion to about 2.5 billion, about 1 billion to about 2 billion exosomes. In further aspects, the unit dosage may comprise about 2 billion to about 5 billion, about 2 billion to about 4.5 billion, or about 2 billion to about 3 billion exosomes. In still other aspects, the unit dosage may comprise about 3 billion to about 4 billion exosomes, from about 3 billion to about 4.5 billion, or about 3 billion to about 5 billion exosomes. In some aspects, the unit dosage may comprise about 4 to 5 billion exosomes.

In further aspects, the unit dosage of the exosome composition may comprise about 15 billion to about 25 billion exosomes. For example, the unit dosage may comprise about 15 billion to about 25 billion, about 15 billion to about 20 billion, about 15 billion to about 18 billion, about 20 billion to about 25 billion, about 23 billion to about 25 billion. In still further aspects, the unit dosage may comprise about 75 billion to about 500 billion exosomes. For example, the unit dosage may comprise about 75 billion to about 450 billion, about 75 billion to about 400 billion, about 75 billion to about 350 billion, about 75 billion to about 300 billion, about 75 billion to about 250 billion, about 75 billion to about 200 billion, about 75 billion to about 150 billion, or about 75 billion to about 100 billion exosomes. In some aspects, the unit dosage may comprise about 100 billion to about 500 billion, about 150 billion to about 500 billion, about 200 billion to about 500 billion, about 250 billion to about 500 billion, about 300 billion to about 500 billion or about 450 billion to about 500 billion exosomes.

In certain aspects, a unit dosage of exosome composition may comprise about 300 billion to about 500 billion exosomes.

In still other aspects, a unit dosage of the exosome composition may comprise about 3 billion exosomes. In some aspects, a unit dosage of the exosome composition may comprise about 10 billion exosomes. In some aspects, a unit dosage of the exosome composition may comprise about 15 billion exosomes.

In some aspects, a unit dosage of the exosome composition may comprise about 100 billion exosomes. In some aspects, a unit dosage of the exosome composition may comprise about 200 billion exosomes. In some aspects, a unit dosage of the exosome composition may comprise about 300 billion exosomes. In some aspects, a unit dosage of the exosome composition may comprise about 400 billion exosomes. In some aspects, a unit dosage of the exosome composition may comprise about 500 billion exosomes.

Also provided herein are MSC compositions comprising one or more mesenchymal stem cells. The MSC compositions provided herein are products of the same method used to derive the exosome compositions as described below. Further the MSC compositions may be provided in one or more unit-dosages each comprising a defined number of mesenchymal stem cells suitable for administration to treat a disease, disorder or condition in a subject in need thereof.

Any compositions described herein (e.g., exosome composition or MSC composition) and any unit dosage of the composition may comprise at least one excipient. Suitable excipients include pharmaceutically acceptable excipients, such as diluents, binders, fillers, buffering agents, pH modifying agents, disintegrants, dispersants, preservatives, lubricants, taste-masking agents, flavoring agents, coloring agents, or combinations thereof. The amount and types of excipients utilized to form pharmaceutical compositions may be selected according to known principles of pharmaceutical science.

In one embodiment, the excipient may be a diluent. The diluent may be compressible (i.e., plastically deformable) or abrasively brittle. Non-limiting examples of suitable compressible diluents include microcrystalline cellulose (MCC), cellulose derivatives, cellulose powder, cellulose esters (i.e., acetate and butyrate mixed esters), ethyl cellulose, methyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, sodium carboxymethylcellulose, corn starch, phosphated corn starch, pregelatinized corn starch, rice starch, potato starch, tapioca starch, starch-lactose, starch-calcium carbonate, sodium starch glycolate, glucose, fructose, lactose, lactose monohydrate, sucrose, xylose, lactitol, mannitol, malitol, sorbitol, xylitol, maltodextrin, and trehalose. Non-limiting examples of suitable abrasively brittle diluents include dibasic calcium phosphate (anhydrous or dihydrate), calcium phosphate tribasic, calcium carbonate, and magnesium carbonate.

In another embodiment, the excipient may be a binder. Suitable binders include, but are not limited to, starches, pregelatinized starches, gelatin, polyvinylpyrrolidone, cellulose, methylcellulose, sodium carboxymethylcellulose, ethylcellulose, polyacrylamides, polyvinyloxoazolidone, polyvinylalcohols, C12-C18 fatty acid alcohol, polyethylene glycol, polyols, or saccharides.

In another embodiment, the excipient may be a filler. Suitable fillers include, but are not limited to, carbohydrates, inorganic compounds, and polyvinylpyrrolidone. By way of non-limiting example, the filler may be calcium sulfate, both di- and tri-basic, starch, calcium carbonate, magnesium carbonate, microcrystalline cellulose, dibasic calcium phosphate, magnesium carbonate, magnesium oxide, calcium silicate, talc, modified starches, lactose, sucrose, mannitol, or sorbitol.

In still another embodiment, the excipient may be a buffering agent. Representative examples of suitable buffering agents include, but are not limited to, phosphates, carbonates, citrates, tris buffers, and buffered saline salts or crystalloid medias (e.g., Tris buffered saline or phosphate buffered saline).

In various embodiments, the excipient may be a pH modifier. By way of non-limiting example, the pH modifying agent may be sodium carbonate, sodium bicarbonate, sodium citrate, citric acid, or phosphoric acid.

In a further embodiment, the excipient may be a disintegrant. The disintegrant may be non-effervescent or effervescent. Suitable examples of non-effervescent disintegrants include, but are not limited to, starches such as corn starch, potato starch, pregelatinized and modified starches thereof, sweeteners, clays, such as bentonite, micro-crystalline cellulose, alginates, sodium starch glycolate, gums such as agar, guar, locust bean, karaya, pecitin, and tragacanth. Non-limiting examples of suitable effervescent disintegrants include sodium bicarbonate in combination with citric acid and sodium bicarbonate in combination with tartaric acid.

In yet another embodiment, the excipient may be a dispersant or dispersing enhancing agent. Suitable dispersants may include, but are not limited to, starch, alginic acid, polyvinylpyrrolidones, guar gum, kaolin, bentonite, purified wood cellulose, sodium starch glycolate, isoamorphous silicate, and microcrystalline cellulose.

In another alternate embodiment, the excipient may be a preservative or cryo-preservative. Non-limiting examples of suitable preservatives or cryo-preservatives include antioxidants, such as BHA, BHT, vitamin A, vitamin C, vitamin E, or retinyl palmitate, citric acid, sodium citrate; chelators such as EDTA or EGTA; Cryo preservatives; such as Dimethyl sulfoxide (DMSO), sugars for preservatives or cryo-preservatives; such as Trehalose, beta-starch, sucrose, and antimicrobials; such as parabens, chlorobutanol, or phenol.

In further aspects, any composition provided herein (e.g., the exosome composition or the MSC composition) may be further processed (e.g., as a powder) using lyophilization. Suitable methods of preparing lyophilized compositions are known in the art. Suitable excipients that may be used to prepare lyophilized compositions may include cryo-preservatives such as Trehalose, beta-starch, and sucralose.

In various aspects, the exosome compositions and the MSC compositions provided herein may be prepared by a method comprising sequentially isolating exosomes and at least one component isolated from an extracellular matrix from a wildtype tissue sample or cell culture comprising mesenchymal stem cells using a tandem tangential flow filtration system. Suitable tandem tangential flow filtration systems and methods of using them are provided below.

II. Methods of Making

Isolation Method

The present method provides substantially undamaged and pure exosomes isolated from a liquid culture of human mesenchymal stem cells. One simplified example ofthis method is summarized in FIG. 1. It is understood that this simplified flow chart may not explicitly list every step useful for obtaining an exosome product.

The MSC culture may be derived from explants of adult and embryonic tissues, such as adipose tissue, muscle, peripheral blood, lung, heart, corneal stroma, dental pulp, placenta, umbilical cord, endometrium, amniotic membrane, and Wharton's jelly, by any method known in the art. For example, MSCs can be obtained from explants of human placental or umbilical cord tissue according to the method of Wu et al. (Scientific Reports (2018) 8:5014). Some exemplary useful MSC tissue sources include uumbilical cord, as MSCs from this tissue have similar immune phenotype and multilineage differentiation, but higher expansion potential relative to bone marrow MSCs and adipose-derived MSCs, and Wharton's jelly. Wharton's jelly (substantia gelatineafuniculi umbilicalis), a gelatinous substance within the umbilical cord, derived from extra-embryonic mesoderm, can be commercially obtained, and MSCs can be isolated from it via e.g., the enzymatic, enzymatic-explant, and explant methods (see, e.g., Vara I (2019) Iran J. Med. Sci. 44(6):437-448).

Liquid MSC cultures of any size can be produced by expanding the original MSC source in a growth medium to any volume which will provide a useful number of exosomes.

The MSCs are removed from the liquid culture by any method known in the art, such as, but not limited to, by centrifugation, gravity filtration, density filtration, syringe filtration, vacuum filtration, column filtration, column chromatography, etc.

For example, the MSCs can be removed from the culture medium by gravity filtration through a prefilter having a pore size of at least 0.4 μm, e.g., about 0.4 μm to about 10 μm. The prefilter can be in the form of a module comprising one or more individual prefilters. For example, the MSC culture medium can be subjected to filtration through a gravity prefilter module comprising a prefilter having a pore size of about 100 μm, followed by a series of prefilters with decreasing pore size, such as a prefilter having a pore size of at least about 0.4 μm, such as about 8.0 μm, about 0.8 μm, and/or about 0.45 μm. These prefilters can be made of any commercially available or other material with the desired pore size, and which does not have any attractive or repulsive characteristics. One nonlimiting, useful prefilter material comprises polypropylene.

The cell-free medium is then processed by tangential flow filtration to obtain the exosomes produced and secreted in the culture medium by the MSCs before the cells are removed from the liquid culture medium. Exosome collection is accomplished by filtering the cell-free culture medium through a commercially obtainable first hollow fiber filter having a pore size of about 0.1 μm to about 1.0 μm to obtain a permeate. For example, the hollow fiber filter maybe a hollow fiber filter having a pore size of about 0.1 μm, about 0.1 μm, about 0.2 μm, about 0.3 μm, about 0.4 μm, about 0.5 μm, about 0.6 μm, about 0.65 μm, about 0.7 μm, about 0.8 μm, about 0.9 μm, or 1.0 μm.

The permeate of the first hollow fiber filter is then subjected to diafiltration through a hollow fiber filter having a pore size of about 30 kD to about 600 kD, about 60 kD to about 600 kD, about 40 kD to about 150 kD, about 60 kD to about 150 kD to obtain a retentate which contains the exosomes. For example, the permeate may be subjected to diafiltration through a second hollow fiber filter tube having a pore size of about 30 kD, about 40 kD, about 50 kD, about 60 kD, about 70 kD, about 80 kD, about 90 kD, about 100 kD, about 110 kD, about 120 kD, about 130 kD, about 140 kD, about 150 kD, about 200 kD, about 250 kD, about 300 kD, about 350 kD, about 400 kD, about 450 kD, about 500 kD, or about 600 kD.

Optionally, the permeate from the first hollow fiber filter may be filtered through an intermediate hollow fiber filter tube have a pore size of about 0.45 μm to about 2.0 μm, about 0.5 μm, about 0.6 μm, about 0.70 μm, about 0.8 μm, about 0.9 μm, about 1.0 μm, about 1.1 μm, about 1.2 μm, about 1.3 μm, about 1.4 μm, about 1.5 μm, about 1.6 μm, about 1.70 sm, about 1.8 μm, about 1.9 μm, or about 2.0 μm to obtain a second permeate which is then subjected to diafiltration through the second hollow fiber filter.

These hollow fiber filters may be in any form, such as, but not limited to, a tube or cassette. These filters comprise polysulfane, polysulfone, and/or “modified” polysulfone, such as, but not limited to, polyethersulfone (see, e.g., (Repligen, Waltham, Mass.) or the addition of amine and/or sulfonyl groups. The final retentate from the second hollow fiber filter comprises or consists substantially of, the collected exosomes.

The amount or yield of exosomes in the retentate can be estimated as follows: A single MSC produces about 1,000 to about 2,200 exosomes per day in a typical MSC growth medium Thus about 3×109 can be obtained from a 15 liter bioreactor MSC culture. For commercial purposes, a useful amount of MSCs are grown to provide a sufficient number of exosome from which a therapeutic product can be made. The present method provides a yield of about 32 trillion to about 50 trillion exosomes from a culture of about 7 billion to about 10 billion mesenchymal stem cells. For example, about 42 trillion exosomes can be expected to be secreted and harvested from about 9×109 MSCs. In another example, from about 10×106 MSCs from an umbilical cord sample, expanded to about 9×106 MSCs secrete into the cell medium of the bioreactor about 42×1012 exosomes before the isolation procedure is initiated.

A dissected sample of the umbilical cord tissue which will be used to obtain MSC exosomes was examined by flow cytometry to see what type of cells were in the sample. This method validates the identity of the cells by detecting the expression of certain expected enzymatic and other antigenic markers on the MSC surface. The dissected tissue sample was then cultured and expanded in a growth medium. A sample of the expanded cell culture medium was then subjected to flow cytometry and examined for the expression of certain MSC surface markers to determine the identity of the cells in the culture. The results, shown in FIG. 2A-2G demonstrate that the expanded cells are MSCs. An exosomal sample from the retentate obtained from this MSC sample was also examined to determined is the exosomes from these MSCs expressed certain expected MSC markers (CD20, CD34, CD45, CD73, CD90, CD105, CD166, and HLA-DR). The results shown in FIGS. 3A-31 indicate that the exosomes do express these markers and thus are viable.

That the MSC exosomes isolated by the present method and system are substantially undamaged and pure can be determined by any exosomal characterization method known in the art, e.g., nanoparticle tracking analysis, exosomal surface marker-based characterization by flow cytometry, fluorescence-activated cell sorting (FACS), Western blotting, enzyme-linked immunosorbent assay (ELISA), MA-based characterization, Tunable Resistance Pulse Sensing (TRPS) characterization. At least some of these methods track the presence of the markers such as CD20, CD34, CD45, CD73, CD90, CD105, CD166, and HLA-DR expected to be on viable exosomes.

Exosome yield can be determined from a sample of the retentate by any method known in the art (see, Koritzinsky (2017) J. Cell Physiol. 232(7):1587-1590), e.g., by particle counting systems such as Izon qEV and TRPS systems, Nanosight's Nanoparticle's Nanoparticle Tracking Analysis, Tunable Resistive Pulse Sensing, by vesicle flow cytometry, Surface Plasmon resonance, or by electron microscopy.

Exosomal Isolation System

The present disclosure also provides a system for obtaining a plurality of exosomes from a source of cell-free MSC culture medium. As disclosed herein, exosomes can be obtained from a cell-free liquid MSC culture by the method and using the system of the present disclosure.

In general, the system may comprise a first tangential flow filter (TFF) in communication with the source of cell-free culture medium. The first TFF generates a retentate and a permeate. The system may further comprise a second TFF. The input of the second TFF is in direct or indirect fluid communication with the permeate of the first TFF. The second TFF also generates a retentate and a permeate, the latter comprising the plurality of exosomes.

Optionally, the presently disclosed system may additionally comprise an intermediate TFF. An input of the intermediate TFF may be in direct or indirect fluid communication with a permeate output of the first TFF and a retentate output of the intermediate TFF may be in direct or indirect fluid communication with the input of the second TFF.

The source of cell-free culture medium may take a variety of forms, including that of a system for prefiltration. Without limitation, the presently disclosed system may or may not include such a system for prefiltration. If employed, the prefiltration system is in communication with the MSC liquid culture and provides the cell-free culture medium.

In addition, the presently disclosed system is not limited by the equipment required or process practiced to achieve the MSC liquid culture.

Various elements useful in implementing the presently disclosed system are also shown and described in illustrative embodiments. For example, feed vessels may be employed for providing fluid input to the first and second TFFs. Various pumps may also be employed to propel fluid throughout portions of the presently disclosed system. Further, a diafiltration reservoir may provide a source of diafiltration buffer with respect to the second TFF.

An optional and illustrative system for obtaining a cell-free mesenchymal stem cell (MSC) liquid culture is described. Human placental and/or umbilical cord tissue is processed according to known techniques in order to isolate MSCs, which are then plated. The cell culture is then harvested prior to introduction into a suitable bioreactor. Cell culture expansion may be repeated as desired or required.

Cell culture expansion occurs in growth medium within the bioreactor for a period of time. In an exemplary embodiment, this time period is five to six days. The cell culture may then be introduced into a subsequent bioreactor containing collection medium for a period of time which, in an illustrative embodiment is three to four days. The MSC culture medium is then collected and processed for cell removal.

An optional and illustrative system for prefiltration of MSCs for cell removal is disclosed, though it is emphasized that a variety of prefiltration equipment may be utilized to achieve satisfactory cell removal results.

The culture introduced to an optional gravity filter which, in one exemplary embodiment, contains a filtered media. Suitable pore sizes may be utilized, and other preliminary filtration techniques may also be practiced, as desired or as necessary.

Next, the MSC culture medium may be passed through a prefilter module. In various aspects, the prefilter module may comprise sequence of discrete prefilters, each having a successively smaller filter pore size. The filtrate of an upstream prefilter is introduced into the subsequent prefilter in order to achieve an ultimate filtrate that is cell-free. Three prefilters are shown, though a different number may be utilized. Alternatively, the illustrated prefilters may be replaced with one or more additional gravity filters or with one or more centrifuge systems.

These prefilters may in one embodiment have filter media formed of polypropylene, and of polypropylene fleece, in particular.

One or more pumps in association the prefilter module may be used due to the small pore size required for cell removal. Thus, in the illustrated embodiment, there is one pump for pumping cell culture into each of the discrete prefilters. These pumps may be, for example, peristaltic pumps.

The cell-free filtered MSC medium is then introduced into a feed vessel. The feed vessel may be provided as a large container having a capacity of, for example, 15 liters. Alternatively, a smaller feed vessel may be employed along with an auxiliary vessel, such as the illustrated bleed vessel. In the illustrated embodiment, the cell-free filtered MSC medium is distributed between these two vessels.

A pump associated with the first feed vessel is then utilized to initially pump the filtered cell-free MSC medium to the input of a first tangential flow filter (TFF). In the illustrated embodiment, the first TFF is a hollow-fiber filter tube (HFT) TFF though other hollow fiber filter formats may be employed as with respect to the first TFF, other hollow fiber filter formats may be employed.

The permeate of the first TFF is accumulated into a collection vessel to form a source of concentrated product. An auxiliary pump may be employed to accumulate the permeate of the first TFF.

Meanwhile, the retentate from the first TFF is recycled into the first feed vessel. If an auxiliary feed vessel is employed for collecting the filtered, cell-free MSC medium, the retentate may be mixed with additional filtered medium. The process of filtering the retentate or combination of retentate and filtered medium continues until a sufficient concentration of permeate has been collected in the collection vessel.

The concentrated product from the permeate of the first TFF may then provided to the input of a second TFF via a second feed vessel. The collection vessel and the second feed vessel may in one embodiment be discrete containers. The collection vessel and the second feed vessel may in one embodiment be the same vessel. The second TFF may be another HFT TFF A pump may be utilized for the purpose of providing the concentrated product from the second feed vessel to the input of the second TFF. This pump, as well as the pump associated with the first feed vessel, may be a peristaltic pump in one non-limiting embodiment

The permeate of the second TFF is directed to a waste container as the product in the retentate is again flowed through the second TFF via the second feed vessel.

A diafiltration reservoir is in fluid communication with the second feed vessel for enabling diafiltration through the second TFF. Diafiltration buffer, such as saline, selectively flows from the diafiltration reservoir into the second feed vessel, replacing the fluid that exits the second TFF as permeate. An auxiliary pump may be utilized to selectively convey the diafiltration buffer into the second feed vessel. Such an auxiliary pump may be a peristaltic pump, for example, though other pump types may be employed.

In an embodiment, the diafiltration reservoir volume is sufficient to retain a volume of diafiltration buffer that is five to ten times the volume of the accumulated, concentrated permeate from the first TFF. Thus, in this embodiment, the second TFF retentate may be washed through five to ten diafiltration volumes (DVs). Other quantities of diafiltration buffer may be employed, however.

Once diafiltration is complete, the second TFF retentate is again recycled to the second feed vessel then back to the input of the second TFF until a desired degree of concentration of the desired exosome product has been achieved. The final product comprising concentrated exosomes is then collected in the second feed vessel. Fluid valves may be utilized to redirect unwanted fluid into a suitable waste container for collection. Another auxiliary pump may be provided for the purpose of waste collection.

Optionally, a third TFF, which may be referred to as an intermediate TFF, may be disposed in fluid communication intermediate the second feed vessel and associated second pump and the second TFF. The intermediate TFF may be an HFT TFF. The output from the second feed vessel is in fluid communication with the input of the intermediate TFF, if used, via the respective pump. The permeate from the intermediate TFF is directed to a waste stream as the product in the retentate of the intermediate TFF is provided to the input of the second TFF, in this alternative embodiment. Diafiltration and concentration, as previously described, thus takes place within the intermediate TFF as well, if used.

The hollow fiber filter tubes of one or more of the first, second, and intermediate TFFs may be provided as polysulfane, polysulfone, and/or modified polysulfone.

A simplified flow chart of the steps involved in utilizing a system described above is provided in FIG. 1. It is understood that this simplified flow chart may not explicitly list every step useful for obtaining an exosome product. For example, the simplified chart does not address use of an intermediate HFT TFF, as discussed above.

In a first step 100, human placental and/or umbilical cord tissue is processed in order to isolate mesenchymal stem cells (MSCs). The MSCs are then cultured and expanded 102, and a cell-free MSC culture medium is obtained therefrom 104, such as through the use of a prefilter module as previously described.

The filtered cell-free culture medium is then concentrated 106 in the permeate of an about 0.1 μm to about 1.0 μm first hollow-fiber filter tube (HFT) tangential flow filter (TFF). This permeate is the conveyed to an about 30 kD to about 600 kD or an about 60 kD to about 150 kD second HFT TFF, where a source of diafiltration buffer enables, for example, a 5 DV to 10 DV diafiltration process 108. Subsequently, the retentate of the second TFF is concentrated to a desired degree and the concentrated retentate is then collected 110 as the final exosome product.

Additional Methods of Preparing Exosome Composition and MSC Compositions

In further aspects of the disclosure, a method of making a composition is provided. As noted, the compositions herein comprise at least one mesenchymal stem cell, at least one exosome isolated from a mesenchymal stem cell, and at least one component isolated from an extracellular matrix. As noted above, the components included in the composition are present at levels much higher than normal (e.g., 5×-100× a concentration found in a comparative exosome preparation, such as one prepared by ultra-centrifugation). Further, none of the cells used in the composition are genetically edited or cultured in any stressful conditions.

In general, methods of preparing the compositions provided herein comprise isolating each component (e.g., mesenchymal stem cell, proteins, lipids, nucleic acids, exosome, and ECM component) separately, using tangential flow filtration, and then recombining to form the final composition.

Accordingly, in one aspect of the present disclosure, a method of preparing an exosome composition and an MSC composition is provided. The method comprises (a) culturing mesenchymal stem cells isolated from a tissue sample in an exosome collection media, (b) collecting the exosome collection media as a first fraction and the mesenchymal stem cells as a second fraction, the second fraction further comprising exosomes and extracellular matrix colonies and fragments thereof, (c) filtering the second fraction through a first section of a tangential flow filtration system to obtain a retentate comprising mesenchymal stem cells and a first filtrate comprising exosomes and the extracellular matrix colonies and fragments thereof, (d) collecting the retentate comprising mesenchymal stem cells as a MSC composition, filtering the first filtrate through a second section of the tangential flow filtration system to form a second retentate comprising the intact and/or partially intact extracellular matrix and a second filtrate comprising exosomes and at least one component from the extracellular matrix, (e) combining the second filtrate with the first fraction to form a third fraction, and (f) collecting the third fraction as the exosome composition.

In various aspects, the method may further comprise filtering the third fraction through a third section of the tangential flow filtration system to form a third filtrate and collecting the third filtrate as the exosome composition. In some aspects, the third filtrate comprises at least one component from the extracellular matrix colonies (e.g., an ECM component), wherein the ECM component is present at a higher concentration in the third filtrate than in the second filtrate.

In still further aspects, the method may further comprise filtering the third filtrate through a fourth section of the tangential flow filtration system to form a fourth filtrate and collecting the fourth filtrate as the exosome composition. In some aspects, the fourth filtrate comprises at least one ECM component present at a higher concentration as compared to the concentration of the component in the third filtrate.

Optionally, the method may further comprise additional steps, where a filtrate obtained in the previous step is filtered through an additional section of the tangential flow filtration system.

In various aspects, the methods may comprise filtering a filtrate through a first section, a second section, a third section, and/or a fourth section of a tangential flow filtration system. In various aspects, the first section comprises a filter having a pore size of about 50 kD to about 100 microns. For example, in some aspects the first section may comprise a filter or cassette comprising a pore size of about 0.1 to 10 microns. In some aspects, the first section may comprise a filter or cassette comprising a pore size of about 0.5 to 1 microns (e.g., about 0.5, 0.6, 0.7, 0.8, 0.9, or 1.0 microns). In some aspects, the second section comprises a filter having a pore size of about 50 kD to about 100 microns. In some aspects, the second section comprises a filter or cassette comprising a pore size of about 50 kD to about 500 kD (e.g., about 100 kD). In further aspects, the third section may comprise a filter having a pore size of about 50 kD to about 100 microns. In some aspects, the third section comprises a filter or cassette comprising a pore size of about 200 to 800 kD (e.g., about 500 kD). In still further aspects, the fourth section may comprise a filter having a pore size of about 50 kD to about 100 microns. Suitable pore sizes that may be used in any of the sections are described further below.

In various aspects, the first section, second section, third section, and/or fourth section, and additional sections/filtration steps as needed, of the tangential flow filtration system may independently comprise a hollow fiber filter or cassette. The hollow fiber filter or cassette may comprise a pore size correlating to the size of the retentate isolated at each section. In some aspects, the pore size is from about 50 kD to about 100 microns. In some aspects, the pore size is about 50 kD to about 1 micron, about 60 kD to about 1 micron, about 40 kD to about 150 kD, about 60 kD to about 150 kD. In some aspects, the hollow fiber filters may have a pore size of about 50 kD, about 60 kD, about 70 kD, about 80 kD, about 90 kD, about 100 kD, about 110 kD, about 120 kD, about 130 kD, about 140 kD, about 150 kD, about 200 kD, about 250 kD, about 300 kD, about 350 kD, about 400 kD, about 450 kD, about 500 kD, or about 600 kD In further aspects and so on, the pore size may be about 700 kD to about 1 micron. In some aspects, the pore size may be about 700 kD, about 750 kD, about 800 kD, about 850 kD, about 900 kD, about 950 kD or about 1 micron. In further aspects, the pore size may be about 1 micron to about 100 microns. For example, the pore size may be about 1 to 2 microns (e.g., about 1.0 micron about 1.1 micron, about 1.2 micron, about 1.3 micron, about 1.4 micron, about 1.5 micron, about 1.6 micron, about 1.7 micron, about 1.8 micron, about 1.9 micron, or about 2.0 micron), about 2-3 micron (e.g., about 2.0 micron, about 2.1 micron, about 2.3 micron, about 2.4 micron, about 2.5 micron, about 2.6 micron, about 2.7 micron, about 2.8 micron, about 2.9 micron, or about 3.0 micron), or about 3-4 micron (e.g., about 3.0 micron, about 3.1 micron, about 3.2 micron, about 3.3 micron, about 3.4 micron, about 3.5 micron, about 3.5 micron, about 3.6 micron, about 3.7 micron, about 3.8 micron, about 3.9 micron or about 4.0 micron). As another example, the pore size may be about 4-5 microns (e.g., about 4.0 micron, about 4.1 micron, about 4.2 micron, about 4.3 micron, about 4.4 micron, about 4.5 micron, about 4.6 micron, about 4.7 micron, about 4.8 micron, about 4.9 micron or about 5.0 micron). In another example, the pore size may be about 5-6 microns (e.g., about 5.0 micron, about 5.1 micron, about 5.2 micron, about 5.3 micron, about 5.4 micron, about 5.5. micron, about 5.6 micron, about 5.7 micron, about 5.8 micron, about 5.9 micron or about 6.0 micron). In still another example, the pore size may be about 6-7 microns (e.g., about 6.0 microns, about 6.1 microns, about 6.2 microns, about 6.3 microns, about 6.4 microns, about 6.5 microns, about 6.6. microns, about 6.7 microns, about 6.8 microns, about 6.9 microns, or about 7.0 microns). As another example, the pore size may be about 7 to 8 microns (e.g., about 7.1 microns, about 7.2 microns, about 7.3 microns, about 7.4 microns, about 7.5 microns, about 7.6 microns, about 7.7 microns, about 7.8 microns, about 7.9 microns or about 8.0 microns and so on). Various other pore sizes (e.g., smaller than 50 kD or larger than 100 microns) may be also contemplated.

Each section of the tangential flow filtration system (e.g., the first section, the second section, the third section and the fourth section or additional sections/filtration steps) may comprise a hollow fiber filter having a pore size specific for that section.

In various aspects, the tissue sample may comprise or may be obtained from umbilical cord blood, placental tissue, umbilical cord tissue, adipose tissue, bone marrow, skin, occular tissue, or teeth. For example, in some aspects, the tissue sample may comprise human placental and/or umbilical cord tissue.

It should also be understood that, unless clearly indicated to the contrary, in any methods claimed herein that include more than one step or act, the order of the steps or acts of the method is not necessarily limited to the order in which the steps or acts of the method are recited.

III. Kits

Various aspects of the present disclosure are directed to kits comprising one or more of the pharmaceutical compositions provided herein. In some aspects, a kit is provided comprising an exosome composition comprising an exosome and at least one component isolated from an extracellular matrix. In some aspects, a kit is provided comprising an MSC composition comprising one or more mesenchymal stem cells. In other aspects, a kit is provided comprising (a) an exosome composition comprising an exosome and at least one component isolated from an extracellular matrix and (b) an MSC composition comprising mesenchymal stem cells.

In any of the kits described herein, the exosome composition may comprise one or more exosomes and one or more components isolated from an extracellular matrix, as described herein. The exosome composition may further comprise a carrier or excipient. In some aspects, the exosome composition may comprise a saline based carrier or excipient. In some aspects, the kit may comprise one or more unit dosages of the exosome composition as provided herein.

In any of the kits described herein, the MSC composition may comprise one or more mesenchymal stem cells. In various aspects, the MSC composition may further comprise a carrier or excipient, as described above. In further aspects, the MSC composition may comprise a saline-based carrier or excipient. In some aspects, the kit may comprise one or more unit dosages of the MSC composition as provided herein.

In various embodiments, the MSC composition may comprise mesenchymal stem cells that are isolated from the same tissue sample used to prepare the exosome composition.

In various aspects, the exosome composition and the MSC composition are provided in a manner to allow for them to be combined prior to administration to a subject.

The kits of this invention are in suitable packaging. Suitable packaging includes preservation and packaging as liquids or powders, but is not limited to, vials, bottles, jars, sheets, flexible packaging (e.g., sealed Mylar or plastic bags), and the like. A kit may have a sterile access port (e.g., the container may be a vial having a stopper pierceable by a hypodermic injection needle).

Kits may optionally provide additional components such as buffers and interpretive information. Normally, the kit comprises a container and a label or package insert(s) on or associated with the container. In some embodiments, the invention provides articles of manufacture comprising contents of the kits described above.

IV. Methods of Use

Further aspects of the present disclosure are directed to methods of treating a subject in need thereof with the compositions provided herein. In various aspects, the methods may comprise administering a first composition comprising at least one exosome and at least one component isolated from an extracellular matrix and a second composition comprising mesenchymal stem cells to a subject. In various aspects, the first composition and the second composition may be prepared and isolated from a single tissue source according to the methods provided above.

In various aspects, the subject may be an individual having or at risk of having any of the following conditions: respiratory and pulmonary diseases or disorders; such as but not limited to cystic fibrosis, pulmonary fibrosis, Chronic Obstructive Pulmonary Disease (COPD), COVID-19 and post COVID-19 symptoms, Arthritis, Avulsions, Plantar Fasciitis, traumatic brain injury or neurological conditions, ophthalmological conditions, Female or Male Reproductive Conditions such as; Polycystic Ovary Syndrome (PCOS) or Primary Ovarian Insufficiency (POI) or Azoospermia or Erectile Dysfunction, Alopecia, Muscular Dystrophy, Autism, cancer, gastrointestinal disorders and diseases, wounds, kidney disease, heart disorders and diseases.

In any of the methods of treatment described herein, the exosome composition and/or the MSC composition may be formulated as pharmaceutical compositions suitable for administration via a route optimal for delivery to a region of the subject affected by the disease or disorder. For example, in various aspects, the pharmaceutical compositions may be administered via injection (e.g., via joint or intramuscular injection) or soft tissue injections. In other aspects, the pharmaceutical compositions may be administered orally or parenterally (e.g., intravenously, subcutaneously, or via infusion). In some aspects, the pharmaceutical compositions may be administered via inhalation.

V. Terminology

The phraseology and terminology employed herein are for the purpose of description and should not be regarded as limiting. For example, the use of a singular term, such as, “a” is not intended as limiting of the number of items. Also, the use of relational terms such as, but not limited to, “top,” “bottom,” “left,” “right,” “upper,” “lower,” “down,” “up,” and “side,” are used in the description for clarity in specific reference to the figures and are not intended to limit the scope of the present inventive concept or the appended claims.

Further, as the present inventive concept is susceptible to embodiments of many different forms, it is intended that the present disclosure be considered as an example of the principles of the present inventive concept and not intended to limit the present inventive concept to the specific embodiments shown and described. Any one of the features of the present inventive concept may be used separately or in combination with any other feature. References to the terms “embodiment,” “embodiments,” and/or the like in the description mean that the feature and/or features being referred to are included in, at least, one aspect of the description. Separate references to the terms “embodiment,” “embodiments,” and/or the like in the description do not necessarily refer to the same embodiment and are also not mutually exclusive unless so stated and/or except as will be readily apparent to those skilled in the art from the description. For example, a feature, structure, process, step, action, or the like described in one embodiment may also be included in other embodiments but is not necessarily included. Thus, the present inventive concept may include a variety of combinations and/or integrations of the embodiments described herein. Additionally, all aspects of the present disclosure, as described herein, are not essential for its practice. Likewise, other systems, methods, features, and advantages of the present inventive concept will be, or become, apparent to one with skill in the art upon examination of the figures and the description. It is intended that all such additional systems, methods, features, and advantages be included within this description, be within the scope of the present inventive concept, and be encompassed by the claims.

As used herein, the term “about,” can mean relative to the recited value, e.g., amount, dose, temperature, time, percentage, etc., +10%, ±9%, ±8%, ±7%, ±6%, ±5%, ±4%, +3%, ±2%, or ±1%.

The terms “comprising,” “including,” “encompassing” and “having” are used interchangeably in this disclosure. The terms “comprising,” “including,” “encompassing” and “having” mean to include, but not necessarily be limited to the things so described.

The terms “or” and “and/or,” as used herein, are to be interpreted as inclusive or meaning any one or any combination. Therefore, “A, B or C” or “A, B and/or C” mean any of the following: “A,” “B” or “C”; “A and B”; “A and C”; “B and C”; “A, B and C.” An exception to this definition will occur only when a combination of elements, functions, steps or acts are in some way inherently mutually exclusive.

The term “treat,” “treated,” “treating,” or “treatment” includes the diminishment or alleviation of at least one symptom associated or caused by the state, disorder or disease being treated. In certain embodiments, the treatment comprises bringing into contact with an infection an effective amount of an anti-infective formulation of the disclosure for conditions related to infections.

As used herein, the term “patient,” “individual,” or “subject” refers to a human or a non-human mammal. Non-human mammals include, but are not limited to, livestock and pets, such as ovine, bovine, porcine, canine, feline, lupine, murine, and marine mammals.

As used herein, the terms “effective amount,” “pharmaceutically effective amount,” and “therapeutically effective amount” refer to a nontoxic but sufficient amount of the purine, purine precursor, purine analog, pyrimidine, pyrimidine precursor, and/or pyrimidine analog to provide the desired biological result. That result may be reduction or alleviation of the signs, symptoms, or causes of a disease, e.g., cancer, or any other desired alteration of a biological system. An appropriate therapeutic amount in any individual case may be determined by one of ordinary skill in the art using routine experimentation.

The terms “culture”, “culture medium”, “cell culture”, and “MSC culture” as used herein refer to a mesenchymal stem cell population that is suspended in a medium under conditions suitable to survival and/or growth of the cell population. These terms as used herein refer to the combination comprising the MSC population and the medium in which the population is suspended.

The terms “medium”, “media”, “culture medium”, and “growth medium” as used herein refer to a substance containing components to support living cells, e.g., nutrients which nourish growing MSCs (i.e., a growth medium), and/or which supports the collection of cells from their expansion or maintenance container (e.g., a collection medium). Typically, these media provide essential and non-essential amino acids, vitamins, energy sources, lipids, and trace elements required by the cell for minimal growth and/or survival. A growth medium can also contain components that enhance growth and/or survival above the minimal rate, including hormones and growth factors. Media are formulated to a pH and salt concentration optimal for cell survival and proliferation. The medium may take any form, such as a solid (as in a petri dish), or liquid.

As used herein, the term “filtrate” refers to the solution and its contents that have passed through a filter.

As used herein, the term “permeate” refers to the solution and its contents that have passed through a membrane filter.

As used herein, the term “retentate” encompasses the components of a solution that have not passed through, and thus are retained by, a membrane filter.

The term “hollow fiber filter (or HFF) as used herein refers to tubes, cassettes, packs, and any container known in the art to contain and comprise hollow fiber filters.

The term “diafiltration” as used herein encompasses a dilution process that involves removal or separation of permeable components (“permeates”) from a solution based on their molecular size with micro-molecule permeable filters in order to obtain a more pure solution. For example, to effectively remove permeate components from solution, fresh solvent may be added to the feed to replace the permeate volume, at the same rate as the permeate flow rate, such that the volume in the system remains constant.

“Tangential flow filtration” (TFF) is a type of filtration in which the majority of the feed flow travels tangentially across the surface of a filter, rather than into the filter. This type of filtration is useful for feeds containing a high proportion of small particle size solids (where the permeate is the product) because solid material can quickly block (blind) the filter surface with dead-end filtration. The term “TFF” also encompasses the filtration device which can be a tube, cassette or any container that comprises one or more hollow fiber filter(s).

The term “prefilter” as used herein is a preliminary filtering element, module, device, or process step or steps used upstream of a membrane filter in order to remove relatively large particulates and to reduce the pressure drop when filtering through one or more downstream membrane filters. The size of the housing needed for downstream membrane filters may thus be reduced.

As used herein, the term “free of” means lacking any or without any.

Having described several embodiments, it will be recognized by those skilled in the art that various modifications, alternative constructions, and equivalents may be used without departing from the spirit of the present inventive concept. Additionally, a number of well-known processes and elements have not been described in order to avoid unnecessarily obscuring the present inventive concept. Accordingly, this description should not be taken as limiting the scope of the present inventive concept.

Those skilled in the art will appreciate that the presently disclosed embodiments teach by way of example and not by limitation. Therefore, the matter contained in this description or shown in the accompanying drawings should be interpreted as illustrative and not in a limiting sense. The following claims are intended to cover all generic and specific features described herein, as well as all statements of the scope of the method and assemblies, which, as a matter of language, might be said to fall there between.

EXAMPLES

The following examples are included to demonstrate preferred embodiments of the disclosure. It should be appreciated by those of skill in the art that the techniques disclosed in the examples that follow represent techniques discovered by the inventor to function well in the practice of the present disclosure, and thus can be considered to constitute preferred modes for its practice. However, those of skill in the art should, in light of the present disclosure, appreciate that many changes can be made in the specific embodiments which are disclosed and still obtain a like or similar result without departing from the spirit and scope of the present disclosure.

Example 1

An umbilical cord was obtained, dissected into tissue samples, washed and stored in PBS in a petri dish. In one experiment, the umbilical cord tissue pieces were placed in a conical tube and colleganase IV was added. The mixture was incubated at 37° C. for 25-36 minutes, which freed the mesenchymal stem cells, allowing for them to be plated in a single cell stack.

In another experiment, the umbilical cord tissue pieces were pulverized using a 40-micron filter which allowed for MSC release into PBS before being placed on a single cell stack.

After MSCs were isolated in a single cell stack, a standard MSC cell expansion media and MSC expansion techniques were used to expand the cells from a single layer cell stack to 10-layer cell stack to 15 liter bio reactor. Then traditional 15-liter bio reactor techniques with media exchange were used until 85% confluency of microcarriers was reached, at which point the media was switched to an exosome collection media for 3 days. After 3 days the exosome collection media was drained and stored, and a lysing technique was used to collect MSCs and their extracellular matrix colonies and materials. Throughout this time, healthy cells were monitored.

The collected mixture (containing MSCs and extracellular matrix colonies and materials) was set aside as one mixture and the exosome collection media (containing exosomes) was set aside as a second mixture. The first mixture (containing MSCs and extracellular matrix colonies and materials) was then applied through a filtration process using a down-stream filter chain and then into a first section of a tangential flow filtration system outfitted with a 0.63-micron hollow fiber filter tube and two peristaltic pumps (one at the feed and one at the permeate). Mesenchymal stem cells were collected in the retentate, and the extracellular matrixes components and exosomes were collected in the permeate. The collected mesenchymal stem cells were stored using cryopreservation medias and freezing techniques for 90-97% viability.

The permeate collected in the first step was then run through a second tangential flow filtration using a 100 kD hollow fiber filter tube which broke up the ECM materials into smaller components and help remove debris. The permeate from this filtration was then combined with the collected exosome media (second mixture) and run through a third tangential flow filtration system using a 500 kD hollow fiber filter tube. The permeate from this last filtration was then run through 500 kD Run 7 diafiltrations exchanging the media for phosphate buffer saline (PBS) before concentrating the material for preparation of pharmaceutical compositions.

Example 2

The exosome composition in Example 1 was analyzed and compared to a commercially available exosome preparation (e.g., AMNIOSOME). Both compositions were analyzed by conventional proteomic techniques. It was found that levels of over 1900 compounds/growth factors/or other components found in extracellular matrix were elevated in the composition of Example 1 compared to levels in the commercially available preparation. (Table 1). Specifically, the following components were found to be elevated at least 30-fold in the pharmaceutical composition relative to the amniosome preparation: Cysteine-rich Protein 1, PIM2, Cadherin-13, Beta IG-H3, EG-VEGF/PK1, Cyclophilin A, Dkk-3, BMP-3, QDPR, PAM, EDAR, EGF R/ErbB1, ALCAM, CXCR3, SBP-1, BCMA/TNFRSF17, CCL28/VIC, IL-29, HSP47, VE-Cadherin, I-309, TGF-beta RiII, CCR8, Fractalkine, TCN1, RSU1, uPAR, VEGF-D, PRELP, TGF-beta RII, Thrombopoietin (TPO), Endothelin, S100A6, Angiogenin, TIMP-4, MSP alpha Chain, Activin A, DMGDH, Serpin B8, TRAIL R3/TNFRSF10C, CFHR5, Caspase-14, PRDX 1, FGF-12, CXCR5/BLR-1, Semaphorin 7A, SPINK7, NT-4, TNF RII/TNFRSF1B, 6Ckine, SerRS, Angiostatin, Angiopoietin-like Factor, B7-1/CD80, Protein C, Tcf20, TROY/TNFRSF19, EMAP-II, CSH1, TLR4, RPLP0, and ErbB3. The following components were found to be elevated at least 40-fold relative to the amniosome preparation: Cysteine-rich Protein 1, PIM2, Cadherin-13, Beta IG-H3, EG-VEGF/PK1, Cyclophilin A, Dkk-3, BMP-3, QDPR, PAM, EDAR, EGF R/ErbB1, ALCAM, CXCR3, and SBP-1. The following components were found to be elevated at least 50-fold relative to the amniosome preparation: Cysteine-rich Protein 1, PIM2, Cadherin-13, Beta IG-H3, EG-VEGF/PK1, and Cyclophilin A.

TABLE 1

Compo-

sition
Comparative
Fold

(Ex. 1)
Product X
Change

Cysteine-rich Protein 1
149,203
1,104
135

PIM2
115,964
1,187
98

Cadherin-13
73,139
1,091
67

Beta IG-H3
80,636
1,254
64

EG-VEGF/PK1
68,881
1,210
57

Cyclophilin A
45,737
846
54

Dkk-3
38,287
784
49

BMP-3
88,015
1,843
48

QDPR
37,451
811
46

PAM
33,225
731
45

EDAR
42,662
958
45

EGF R/ErbB1
41,416
933
44

ALCAM
61,608
1,467
42

CXCR3
66,674
1,645
41

SBP-1
32,293
806
40

BCMA/TNFRSF17
37,102
976
38

CCL28/VIC
78,792
2,078
38

IL-29
42,551
1,127
38

HSP47
20,436
546
37

VE-Cadherin
26,081
708
37

I-309
34,480
938
37

TGF-beta RIII
24,023
661
36

CCR8
52,976
1,464
36

Fractalkine
29,902
843
35

TCN1
37,005
1,052
35

RSU1
32,106
921
35

uPAR
22,952
663
35

VEGF-D
23,224
687
34

PRELP
36,022
1,074
34

TGF-beta RII
21,509
642
33

Thrombopoietin (TPO)
21,818
652
33

Endothelin
27,732
830
33

S100A6
40,864
1,224
33

Angiogenin
47,702
1,435
33

TIMP-4
20,307
611
33

MSP alpha Chain
38,530
1,163
33

Activin A
54,561
1,665
33

DMGDH
134,640
4,139
33

Serpin B8
27,810
865
32

TRAIL R3/TNFRSF10C
20,997
657
32

CFHR5
34,102
1,068
32

Caspase-14
39,469
1,251
32

PRDX 1
42,240
1,349
31

FGF-12
34,839
1,120
31

CXCR5/BLR-1
58,132
1,878
31

Semaphorin 7A
24,942
807
31

SPINK7
21,269
691
31

NT-4
31,028
1,011
31

TNF RII/TNFRSF1B
19,548
638
31

6Ckine
52,082
1,700
31

SerRS
34,859
1,145
30

Angiostatin
48,636
1,602
30

Angiopoietin-like Factor
18,397
608
30

B7-1/CD80
32,128
1,068
30

Protein C
35,349
1,184
30

Tcf20
29,604
992
30

TROY/TNFRSF19
17,905
600
30

EMAP-II
39,423
1,324
30

CSH1
30,240
1,018
30

TLR4
18,946
639
30

RPLP0
29,025
983
30

ErbB3
39,907
1,352
30

RPL11
23,521
800
29

PGK-1
30,469
1,036
29

FGF-16
51,205
1,742
29

Plakophilin 1
27,751
949
29

PRCP
35,799
1,224
29

RAGE
26,777
919
29

Insulin
18,388
632
29

TSR2
21,530
740
29

NT-3
31,941
1,106
29

USP14
19,830
689
29

VDAC1/Porin
22,828
797
29

Proteasome 20S a + b
34,141
1,198
28

M-CSF
33,014
1,162
28

IL-2
39,782
1,401
28

ICAM-1
33,591
1,185
28

NEDD8
40,984
1,450
28

PRG2
25,365
904
28

Insulysin/IDE
25,461
908
28

ICAM-2
24,504
883
28

MMP-1
24,507
884
28

Salivary alpha amylase/aAmylase
25,763
933
28

IL-17F
29,785
1,085
27

Galectin-1
24,936
912
27

Lymphotoxin beta/TNFSF3
40,746
1,492
27

TBCA
29,394
1,079
27

PREP
30,057
1,108
27

VAP-A
20,295
750
27

Utrophin
18,967
701
27

YB1
18,400
684
27

VAP-1
22,983
858
27

CFHR4
46,661
1,745
27

FGF-20
22,187
831
27

Cyclophilin B
48,270
1,811
27

RNASE4
29,155
1,095
27

SBSN
29,412
1,105
27

FGF R4
44,618
1,677
27

FGF-17
30,774
1,167
26

PGLS-C-t
31,449
1,201
26

Eotaxin-3/CCL26
37,851
1,450
26

RREB1
19,521
749
26

TMEM223
19,299
742
26

ADAMTS-15
17,976
696
26

Semenogelin II/SEMG2
29,002
1,127
26

C3a
40,536
1,589
26

RPL12
21,195
831
25

GDF8
29,382
1,155
25

IGF-II
25,799
1,017
25

RPS25
20,252
799
25

Follistatin-like 1
28,349
1,121
25

Smad 5
16,806
665
25

Notch-2
33,545
1,327
25

I-TAC/CXCL11
32,382
1,282
25

TRANCE
22,237
882
25

MMP-3
23,176
920
25

uPA
18,676
742
25

WDR1
20,309
807
25

UQCRB
18,808
755
25

DR6/TNFRSF21
25,103
1,014
25

BMP-15
30,067
1,214
25

PSMA4
32,129
1,298
25

ErbB4
42,960
1,737
25

Gephyrin
39,752
1,615
25

beta-NGF
48,014
1,952
25

BMP-2
42,980
1,749
25

BMP-6
28,712
1,169
25

NAP-2
23,985
978
25

LECT2
23,752
974
24

FGF-13 1B
27,960
1,153
24

Reg3A
25,684
1,061
24

CD14
37,782
1,561
24

SHIP
24,658
1,020
24

RPL5
20,382
844
24

VEGF
16,527
687
24

IL-1 F5/FIL1delta
32,327
1,344
24

RPS28
23,823
991
24

TUBA6
20,864
868
24

Endostatin
33,106
1,378
24

MMP-9
34,631
1,443
24

CK-MB
30,019
1,255
24

CapG
47,296
1,982
24

IL-11
30,940
1,298
24

Ribonuclease A
30,250
1,272
24

Eotaxin-2/MPIF-2
28,293
1,191
24

GLO-1
17,986
758
24

TLR3
14,894
628
24

HGF
32,924
1,390
24

Sterol carrier protein 2/SCP2
24,330
1,027
24

Visfatin
21,155
900
24

SHC1
29,841
1,279
23

IL-18 R beta/AcPL
35,493
1,522
23

SIGLEC14
17,357
745
23

PRTN3
29,438
1,263
23

Contactin-1
22,064
947
23

CV-2/Crossveinless-2
27,932
1,200
23

EDG-1
60,140
2,592
23

CXCL14/BRAK
44,202
1,905
23

TIMP-3
18,709
807
23

Serpin A1
26,893
1,162
23

Annexin A1
36,102
1,561
23

TGM3
21,623
936
23

CXCR6
40,642
1,759
23

PGM1
30,176
1,307
23

Osteoprotegerin/TNFRSF11B
31,132
1,354
23

Coagulation Factor III/Tissue
24,385
1,061
23

Factor

M-CSF R
27,715
1,208
23

MDC
19,302
849
23

FAM3B
27,761
1,221
23

MMP-11/Stromelysin-3
28,775
1,267
23

SCF R/CD117
30,514
1,344
23

TGF-beta 5
33,193
1,467
23

Titin
19,113
845
23

sFRP-3
14,536
643
23

IL-1 beta
31,067
1,382
22

HCC-4/CCL16
31,885
1,420
22

TRAIL/TNFSF10
15,890
708
22

Fascin
29,829
1,330
22

BNP
56,464
2,518
22

ADAMTS-13
16,762
751
22

PLOD1
22,859
1,024
22

FLRG
23,149
1,039
22

LDHA
33,197
1,492
22

LIF
22,784
1,024
22

YY1
23,334
1,051
22

NME3
29,412
1,326
22

ESAM
23,809
1,075
22

RPS19
22,292
1,007
22

EpCAM
26,880
1,215
22

TAGLN2
20,278
917
22

CXCL16
25,046
1,133
22

BTF3
29,870
1,352
22

Hemoglobin subunit beta/HBB
32,091
1,453
22

TRADD
22,568
1,022
22

Metavinculin
24,036
1,090
22

BDNF
38,489
1,752
22

Galectin-7
23,599
1,075
22

PPP2R4
29,134
1,328
22

FACX
26,222
1,198
22

PDZD2
25,371
1,160
22

IL-26
30,655
1,402
22

FGF-9
29,601
1,354
22

Fibrinogen-like 2
26,901
1,231
22

Plexin B2
33,435
1,533
22

Thrombomodulin
26,841
1,234
22

Dtk
31,635
1,455
22

TRAIL R2/DR5/TNFRSF10B
21,922
1,009
22

PNP
34,355
1,581
22

ANGPTL8
32,467
1,497
22

B7-H3
46,713
2,154
22

ACLP
50,429
2,328
22

Galectin-3
24,906
1,150
22

p73
27,714
1,280
22

IL-4
35,063
1,620
22

IL-13 R alpha 2
26,900
1,243
22

TOB2
27,179
1,257
22

Claudin-3
27,121
1,256
22

IL-8
29,634
1,374
22

VEGF-C
18,712
868
22

IGF-I SR
30,199
1,406
21

Tenascin X(1)
24,673
1,150
21

Lefty - A
24,434
1,141
21

Thrombospondin-1
37,063
1,732
21

OSM R beta
29,453
1,376
21

SUCLG1
21,081
986
21

PDGF-AB
25,932
1,214
21

IL-6 R
29,897
1,406
21

IL-18 BPa
31,825
1,497
21

PGAM2
27,086
1,276
21

Cripto-1
28,401
1,338
21

FGF-23
27,823
1,311
21

GSTM1
32,803
1,549
21

ICAM-5
29,071
1,374
21

RPL10
17,000
804
21

Ribonuclease Inhibitor
30,183
1,430
21

ARTS1
50,156
2,381
21

Periostin
26,741
1,274
21

UCH-L1
19,573
933
21

Zyxin
8,465
404
21

RPL10A
20,817
995
21

PDLIM5
22,539
1,078
21

IL-15 R alpha
27,140
1,302
21

FAM3C
34,874
1,679
21

Tropomyosin 3
21,960
1,058
21

LZTS1
21,074
1,016
21

LIGHT/TNFSF14
29,147
1,406
21

Osteoadherin(2)
25,234
1,219
21

SHMT1
20,473
990
21

CCR9
37,245
1,809
21

TWEAK R/TNFRSF12
14,437
702
21

TPP1
22,445
1,098
20

ADAMTS-10
17,984
881
20

RCL
18,903
926
20

PCDH7
20,445
1,004
20

MIG
21,444
1,053
20

SPARC
24,373
1,197
20

SH3BGRL
25,017
1,230
20

Thrombospondin-4
21,067
1,036
20

UFM 1
22,515
1,107
20

Prostaglandin D Synthase/PTGDS
39,363
1,938
20

GPR-39
23,460
1,158
20

SPTBN1
27,815
1,375
20

BLVRB
26,728
1,322
20

RKIP
21,651
1,072
20

4-1BB
14,926
739
20

Decorin
34,993
1,734
20

CRIM 1
34,092
1,692
20

PCSK9
19,231
955
20

STI1
17,991
893
20

IL-22 BP
26,510
1,317
20

VEGF R2 (KDR)
14,133
702
20

Ficolin-2
26,276
1,306
20

CXCR4 (fusin)
33,542
1,667
20

SIGIRR
30,497
1,518
20

IFN-beta
33,101
1,649
20

Cyclin D1
25,037
1,248
20

MIP-1a
31,294
1,561
20

RPS11
24,126
1,203
20

Alpha 1 AG
25,755
1,285
20

BLAME
25,805
1,290
20

Cystatin E/M
41,616
2,083
20

GM-CSF R alpha
35,942
1,807
20

Uteroglobin(1)
28,383
1,428
20

Trypsinogeb-2
20,582
1,039
20

MCP-3
25,066
1,269
20

Erythropoietin R
17,635
893
20

Proteasome subunit alpha type
30,603
1,551
20

6/PSMA6

TGF-alpha
13,668
693
20

Flt-3 Ligand
35,206
1,785
20

Nanog
17,758
901
20

TNF-alpha
22,873
1,160
20

Spectrin beta-5
14,067
716
20

VNN1
16,972
866
20

BMP-1
43,662
2,229
20

FGF-7/KGF
35,563
1,816
20

OSM
25,688
1,312
20

FGF R5
29,164
1,490
20

Transferrin
26,482
1,355
20

C5/C5a
38,410
1,973
19

ApoA1
41,149
2,114
19

TCP1 eta
25,301
1,300
19

Galectin-3BP
21,938
1,128
19

PTPRZ
24,708
1,271
19

TRAIL R1/DR4/TNFRSF10A
24,139
1,242
19

Six3
22,081
1,136
19

SORD
16,563
852
19

CNTF
39,429
2,031
19

GDNF
25,969
1,338
19

BMPR-II
38,836
2,001
19

CXCR2/IL-8 RB
35,362
1,826
19

FGF-8
26,215
1,354
19

RPS5
23,251
1,201
19

CRF21
39,007
2,017
19

PGDF/PHGDH
29,041
1,508
19

FABP1
19,541
1,016
19

SLURP1
19,488
1,014
19

CEACAM-8/CD66b
29,257
1,522
19

UNC45A
21,825
1,136
19

Adiponectin/Acrp30
35,677
1,858
19

MMP-25/MT6-MMP
25,009
1,303
19

SMC4
24,657
1,285
19

Ornithine Carbamoyltransferase/
24,463
1,276
19

OTC

IFN-gamma R1
26,894
1,403
19

CCR4
30,115
1,572
19

Proteasome beta 1
21,271
1,110
19

Talin1&2
16,845
880
19

Prohibitin
24,124
1,263
19

MMP-24/MT5-MMP
16,935
887
19

SP-D
18,470
968
19

Nidogen-2
18,104
949
19

PTPRS
21,753
1,140
19

SIRP beta 1/CD172b
25,241
1,324
19

APRIL
32,749
1,718
19

ACE-2
15,239
800
19

IL-6
27,278
1,432
19

HGFA
22,952
1,205
19

E-Selectin
36,240
1,904
19

GATA-4
13,311
700
19

VEGF R3
12,540
659
19

UBE2D3
17,721
932
19

BAFF R/TNFRSF13C
18,757
988
19

Layilin
24,229
1,276
19

Cytokeratin 8
24,133
1,272
19

Profilin 1
24,560
1,295
19

Cathepsin B
19,271
1,017
19

Marapsin
22,510
1,192
19

Lymphotactin/XCL1
24,415
1,295
19

Nidgen-1
19,502
1,034
19

MEP1A
28,519
1,517
19

MIF
26,873
1,431
19

IL-1 F8/FIL1 eta
27,935
1,489
19

MMP-14
30,203
1,612
19

HB-EGF
18,456
985
19

Latent TGF-beta bp1
28,019
1,496
19

C8B
20,017
1,069
19

SMPD4
31,555
1,686
19

ADAMTS-18
15,184
812
19

FGF Basic
28,278
1,513
19

IL-12 R beta 2
17,252
924
19

MINPP1
27,616
1,482
19

URP2
22,612
1,215
19

Glycoprotein V
16,534
889
19

LRG1
31,287
1,682
19

ACPP
16,111
867
19

AlphaA Crystallin/CRYAA
24,080
1,296
19

EDA-A2
24,511
1,322
19

SH3BGRL3
22,561
1,218
19

Serpin F2
17,117
924
19

CD40 Ligand/TNFSF5/CD154
35,727
1,930
19

CPEB3
46,158
2,494
19

A2M
18,901
1,023
18

Activin B
26,203
1,419
18

SREC-II
18,431
999
18

EGF
31,100
1,690
18

FGF-19
18,449
1,003
18

Myoferlin
30,277
1,650
18

Endoglin/CD105
29,311
1,600
18

RECK
18,747
1,024
18

ADAM-9
16,548
906
18

SSEA-4
25,424
1,394
18

DDAH1
33,804
1,855
18

P-Cadherin
21,295
1,169
18

IL-22 R
20,435
1,122
18

Glut1
19,737
1,084
18

Symplekin
23,473
1,290
18

S100A11
21,413
1,179
18

SLITRK1
18,859
1,038
18

GCP-2/CXCL6
24,874
1,370
18

SDPR
22,304
1,229
18

IGF-II R
19,162
1,056
18

P4HB
16,222
894
18

TNF-beta
22,047
1,216
18

IL-1 R8
16,408
905
18

IL-1 alpha
29,639
1,635
18

Angiopoietin-4
20,410
1,127
18

TCCR/WSX-1
14,285
790
18

GITR/TNFRF18
30,793
1,707
18

ILK
35,633
1,977
18

TCEB2
25,563
1,418
18

RPL22
17,962
997
18

DEP-1
34,996
1,943
18

FGF-18
26,774
1,487
18

TL1A/TNFSF15
10,943
608
18

EphA6
14,218
792
18

IL-36RN
18,076
1,007
18

Tarc
17,311
964
18

UROC1
27,121
1,513
18

Activin C
31,896
1,781
18

FASN
29,363
1,640
18

PYGL
20,205
1,129
18

Somatostatin
16,925
947
18

Musk
30,581
1,714
18

PLA2G1B
17,499
983
18

IL-1 R3/IL-1 R AcP
14,778
831
18

FGF-6
32,671
1,838
18

IL-18 R alpha/IL-1 R5
32,067
1,809
18

Tie-2
11,507
650
18

NIT2
20,309
1,147
18

PF4/CXCL4
33,866
1,912
18

TPM1
14,914
843
18

GDF11
28,943
1,637
18

IGFBP-6
19,742
1,119
18

Thymopoietin
21,289
1,207
18

FUCA1
17,656
1,002
18

CRHBP
40,876
2,322
18

C1qR1
37,195
2,115
18

STAT3
16,077
914
18

TPM4
39,149
2,227
18

Follistatin
36,797
2,093
18

Laminin b2
27,191
1,548
18

IL-1 sRI
26,575
1,515
18

CCR7
32,601
1,862
18

ApoA2
48,654
2,789
17

ENA-78
34,130
1,958
17

Myosin 18B
32,665
1,878
17

Desmoplakin
16,073
924
17

Neurabin 1
26,374
1,521
17

FGF-4
28,997
1,676
17

PDGF-BB
18,974
1,097
17

PCBP2
26,143
1,513
17

P20Sb3
36,319
2,104
17

IGF2BP1
19,793
1,149
17

Chardin-Like 2
21,410
1,243
17

UNC-13 Homolog D
13,832
803
17

Enolase 2
21,979
1,279
17

Angiopoietin-2
45,909
2,675
17

TFF2(1)
17,923
1,046
17

RHOC
24,067
1,405
17

SUMO3
20,328
1,187
17

DGK
34,594
2,022
17

HVEM/TNFRSF14
25,243
1,478
17

GRO-a
28,801
1,687
17

GALNT2
19,977
1,170
17

TECK/CCL25
10,167
596
17

Notch-1
20,356
1,194
17

Cystatin S
42,547
2,496
17

IL-2 R alpha
25,984
1,528
17

WNK2
19,530
1,149
17

eIF5A
23,678
1,393
17

TrypsinPan
15,201
895
17

SCF
15,181
894
17

CD30/TNFRSF8
30,200
1,783
17

IL-1 F6/FIL1 epsilon
21,801
1,288
17

CutA
16,929
1,001
17

CFL1
53,170
3,147
17

TRAIL R4/TNFRSF10D
12,702
752
17

MBD2
27,960
1,656
17

UBE2N/Ubc13
13,689
812
17

PI 16
25,837
1,535
17

DANCE
18,184
1,081
17

FABP2
17,989
1,070
17

IGFBP-4
39,803
2,369
17

NEP
17,317
1,032
17

NRG1 Isoform GGF2
14,516
865
17

IL-2 R gamma
31,605
1,887
17

MAC-1
25,526
1,527
17

MPO
22,503
1,348
17

SerpinE2
16,518
989
17

GDF1
16,860
1,010
17

IL-17
21,768
1,305
17

Orexin A
10,971
658
17

Kremen-1
18,568
1,116
17

Smad 4
15,672
943
17

IL-17B R
34,269
2,062
17

GCSF
21,209
1,278
17

Annexin V
20,977
1,265
17

IL-31
11,753
709
17

TRAP1
15,849
956
17

Transketolase/TALDO
32,472
1,961
17

pIgR
19,122
1,156
17

Brg1
22,575
1,368
17

BMX
24,657
1,494
17

MAN1
22,070
1,338
17

Orosomucoid 2
19,532
1,184
16

RAP1AB
19,947
1,211
16

VEGF-B
10,517
638
16

SLC38A10
19,397
1,178
16

RPS2
37,085
2,255
16

RANTES
16,051
977
16

SerpinB4
22,437
1,368
16

Nestin
18,097
1,104
16

Complement factor H
18,375
1,121
16

MAPRE1
21,932
1,342
16

PDGF-AA
13,401
820
16

Reg1A
19,797
1,212
16

MUCDHL
26,042
1,598
16

SSTR2
18,703
1,148
16

IGSF4B
27,949
1,715
16

TSG-6
17,133
1,052
16

Orexin B
20,216
1,241
16

Quiescin Q6
16,451
1,011
16

IGFBP-2
26,798
1,650
16

IGFBP-rp1/IGFBP-7
24,778
1,526
16

Dystroglycan
13,218
815
16

Alanine Transaminase/ALT
25,516
1,574
16

FKBP12
25,229
1,557
16

Growth Hormone R (GHR)
25,979
1,605
16

MCP-1
19,729
1,219
16

IL-21
28,485
1,761
16

RANK/TNFRSF11A
19,561
1,209
16

HRG-beta 1
15,425
956
16

ACTC1
25,104
1,556
16

Ribonuclease T2
27,410
1,704
16

B3GNT1
19,695
1,227
16

Src(1)
17,973
1,120
16

PCYOX1
24,219
1,510
16

Leptin R
18,188
1,135
16

IL-19
27,739
1,731
16

CXCR1/IL-8 RA
30,943
1,934
16

PTP mu
19,280
1,205
16

IL-1 ra
26,190
1,638
16

PDGF-D
12,237
766
16

HEXB
28,675
1,797
16

ERp57
10,408
652
16

PLC-gamma 1
28,243
1,771
16

Nesprin2
24,670
1,549
16

Frizzled-4
13,223
831
16

B7-H2
32,439
2,040
16

NAGLU
25,670
1,615
16

Serpin B5
17,301
1,089
16

TNF RI/TNFRSF1A
11,769
741
16

IL-1 F9/IL-1 H1
25,411
1,601
16

Histone H2B K
28,635
1,806
16

OX40 Ligand/TNFSF4
23,345
1,472
16

Aminoacylase
21,552
1,359
16

Transaldolase 1/TALDO1
16,347
1,031
16

Glucagon
18,450
1,165
16

IFRD1
22,022
1,391
16

sFRP-4
14,350
908
16

IL-22
21,050
1,336
16

Kininostatin/kininogen
15,823
1,005
16

PRDM13
17,370
1,103
16

CCR5
25,092
1,595
16

C 1q
39,845
2,534
16

AMPKa1
16,149
1,027
16

EXTL2
44,559
2,837
16

POR
19,330
1,232
16

Smad 8
11,139
710
16

TXNDC5
14,242
908
16

IL-17RD
15,672
999
16

TREM-1
12,193
778
16

SDNSF
14,563
930
16

FKBP51
30,620
1,956
16

Complement Factor B
24,127
1,543
16

Cadherin-6
26,023
1,665
16

VCAM-1 (CD106)
15,111
967
16

11b-HSD1
11,665
747
16

Tie-1
13,154
844
16

Vimentin B
11,807
758
16

DISC 1
33,237
2,133
16

RPL7A
24,850
1,601
16

GDF-15
20,531
1,327
15

IL-31 RA
11,224
726
15

IL-5 R alpha
25,954
1,678
15

p16 ARC
24,766
1,602
15

EN-RAGE
17,256
1,117
15

Biglycan
15,120
979
15

DSCAM
22,416
1,452
15

Aggrecan
32,132
2,082
15

DCI
26,785
1,736
15

Cathepsin A
23,000
1,491
15

HGFR
17,385
1,128
15

sFRP-1
12,564
816
15

IL-4 R
20,838
1,354
15

IL-5
26,138
1,699
15

FGF R3
31,561
2,052
15

Activin RIA/ALK-2
28,753
1,871
15

Prdx6
17,676
1,150
15

Cathepsin L
13,724
894
15

Ezrin
26,184
1,706
15

TAX1BP3
69,739
4,554
15

FGF-BP
31,586
2,066
15

AMICA
12,793
838
15

KMD4B
21,577
1,414
15

Artemin
19,573
1,283
15

Axl
29,155
1,912
15

Claudin-4
17,268
1,135
15

SDF-1/CXCL12
26,062
1,715
15

FADD
15,311
1,008
15

MAP1A
24,358
1,604
15

ABCF1
28,594
1,891
15

Annexin A6
33,758
2,234
15

G-CSF R/CD 114
24,480
1,622
15

TSLP R
8,816
584
15

BRCA 2
24,901
1,653
15

EphA2
18,638
1,241
15

Cystatin SN
32,506
2,164
15

Fas Ligand
24,013
1,600
15

Pappalysin-1
15,261
1,018
15

ME1
28,283
1,887
15

2B4
11,020
735
15

Fe RIIB/C
16,687
1,117
15

Dkk-4
28,306
1,895
15

alpha-Synuclein
28,760
1,927
15

Neural Cadherin
33,750
2,265
15

ANGPTL3
22,632
1,520
15

C 1q S
33,191
2,232
15

ATBF1/ZFHX3
31,056
2,089
15

IGF-I
20,986
1,412
15

IL-3
19,203
1,292
15

IL-3 R alpha
23,009
1,549
15

Semaphorin 6B
22,347
1,504
15

DPPIV
16,714
1,126
15

LAMP2
32,187
2,169
15

Angiopoietin-like 1
32,815
2,211
15

ERAP2
19,198
1,294
15

PCDX8
20,443
1,378
15

ALKP
19,849
1,339
15

TMEFF2
9,761
659
15

IFN-alpha/beta R2
14,863
1,003
15

STOM
35,805
2,418
15

HSP20
17,410
1,176
15

Ck beta 8-1
13,926
941
15

IL-2 R beta/CD122
26,777
1,809
15

NrCAM
24,989
1,690
15

MMRN1
17,082
1,157
15

OSCAR
25,990
1,761
15

IL-21 R
16,314
1,106
15

PTMA
26,420
1,792
15

BLMH
20,162
1,368
15

PLS3
28,956
1,965
15

IL-10
21,240
1,442
15

CPM
32,328
2,197
15

cIAP-2
11,722
797
15

Pref-1
22,136
1,508
15

GASP-1/WFIKKNRP
25,644
1,747
15

FAP
16,380
1,118
15

Fibrinogen
42,805
2,922
15

PPCS
18,634
1,272
15

LFA-1 alpha
16,196
1,106
15

Mcl-1
27,582
1,887
15

DcR3/TNFRSF6B
26,742
1,830
15

Mesothelin
15,354
1,052
15

TACI/TNFRSF13B
28,735
1,973
15

Chemerin
17,506
1,202
15

WISP2
23,342
1,607
15

GM-CSF
18,296
1,261
15

DLL4
14,364
991
14

TLS/FUS
14,659
1,012
14

AGA
17,036
1,177
14

BTC
30,096
2,080
14

Chromogranin B
20,797
1,439
14

HMGB3
19,679
1,362
14

CFVII
29,061
2,017
14

Cryptic
28,697
1,993
14

CCR6
24,127
1,676
14

CrkL
20,032
1,393
14

14-3-3 beta
16,975
1,182
14

TGF-beta RI/ALK-5
8,778
612
14

EphA1
24,362
1,699
14

Trypsin 1
18,179
1,268
14

Lipocalin-1
22,281
1,557
14

Podocalyxin
19,415
1,357
14

sgp130
21,215
1,484
14

Lipocalin-2
18,380
1,286
14

Caspase-3
11,632
815
14

ITIH4 a
18,698
1,310
14

FSH
16,769
1,175
14

Ras
12,226
857
14

PTP kappa
17,441
1,227
14

TIMP-1
11,955
843
14

Calsyntenin-1
14,735
1,040
14

MARCKS
23,174
1,636
14

ARP19
17,822
1,261
14

Fibronectin
21,800
1,544
14

Activin RIB/ALK-4
27,338
1,936
14

Chitobiase
34,121
2,419
14

OSBP1
25,462
1,805
14

IL-23
11,722
831
14

IL-12 R beta 1
24,178
1,715
14

GCSH
38,747
2,749
14

PLOD2
17,373
1,233
14

Nectin-3
21,640
1,537
14

GRP75
15,350
1,091
14

Soggy-1
21,783
1,548
14

MIP-3 alpha
12,400
881
14

GFR alpha-4
26,319
1,876
14

HMGB1
24,395
1,741
14

PCK2
25,024
1,786
14

LRP-1
19,282
1,378
14

MMP-8
24,721
1,767
14

HSP70
21,327
1,526
14

EPCR
26,477
1,894
14

Epiregulin
23,195
1,660
14

Gas1
17,800
1,275
14

CTLA-4/CD152
28,714
2,058
14

IL-27
12,538
899
14

TGF-beta 1
22,019
1,583
14

Attractin
15,292
1,099
14

BNIP2
20,774
1,495
14

BMP-5
21,307
1,535
14

PKLR
23,555
1,698
14

CCR3
26,579
1,916
14

Histone H2A
15,496
1,118
14

PDGF-C
13,580
980
14

IL-17B
27,758
2,005
14

Osteoactivin/GPNMB
17,750
1,284
14

CPE
23,356
1,690
14

CD40/TNFRSF5
25,587
1,853
14

CA1
32,731
2,371
14

Triosephosphate isomerase/TPIS
8,857
642
14

ADAMTS-17
18,090
1,312
14

EYA2
21,449
1,557
14

GFR alpha-1
15,007
1,089
14

Amylin
41,786
3,036
14

DMP-1
13,760
1,001
14

NUP98
24,583
1,788
14

SERPING1
19,916
1,451
14

CKB
31,492
2,297
14

CCR2
16,385
1,195
14

pro-MMP13
11,194
817
14

ApoC1
21,874
1,596
14

Glucose 6 Phosphate
33,245
2,426
14

Dehydrogenase/G6PD

Caldesmon/CALD1
27,072
1,979
14

TLR2
9,606
702
14

NGF R
15,861
1,160
14

PSA-Free
19,062
1,395
14

COCO
17,843
1,307
14

MRP 1
24,512
1,797
14

MCAM
29,993
2,203
14

GRP78
19,150
1,410
14

IL-9
23,601
1,738
14

IL-1 R9
16,172
1,194
14

NAIP
21,107
1,559
14

RBP4
18,599
1,374
14

PABP
23,000
1,701
14

CEACAM-1
14,087
1,043
14

ADAMTS-5
22,125
1,639
13

ALPP
27,361
2,028
13

GPX1
14,338
1,064
13

Cathepsin X/Z/P
24,495
1,819
13

ApoB
13,243
984
13

Contactin-2
17,865
1,329
13

LRP-6
12,871
959
13

MMP-2
21,512
1,603
13

MFRP
17,695
1,321
13

Survivin
14,394
1,077
13

Siglec-1
12,748
954
13

PD-ECGF
27,988
2,094
13

cTnT
21,985
1,645
13

Thioredoxin-1
18,018
1,350
13

PGD
24,343
1,824
13

RPS23
12,653
949
13

TPX
15,924
1,194
13

LAMP
21,609
1,624
13

Myotrophin
23,751
1,786
13

SSTR5
15,956
1,200
13

IP-10
18,137
1,365
13

PGRPL
28,556
2,151
13

GDF7
35,383
2,666
13

FAM20C
21,716
1,638
13

ARFBP1
66,135
4,993
13

Activin RIIA
23,804
1,799
13

Sonic Hedgehog (Shh N-terminal)
23,283
1,760
13

ApoC2
11,918
901
13

CFI
34,438
2,606
13

Adipsin
17,643
1,335
13

C7
23,445
1,777
13

ApoM
10,437
791
13

HRG
19,505
1,482
13

Fibulin 3
21,023
1,597
13

HINT1
20,694
1,573
13

GPBB
17,496
1,335
13

GDF5
32,503
2,485
13

Histone H1.3
16,018
1,226
13

RELM beta
15,967
1,223
13

glutathione S transferase Omega
20,548
1,575
13

1/GSTO1

Serpin A3
18,682
1,433
13

ErbB2
22,810
1,751
13

XIAP
13,150
1,010
13

IBSP
13,928
1,070
13

MICA
18,327
1,409
13

Desmocollin-3
12,281
944
13

Prolactin
24,655
1,896
13

Leptin (OB)
15,996
1,232
13

WISP-1/CCN4
12,639
974
13

Aldolase B
12,926
997
13

NPAS3
21,153
1,635
13

LOX-1
12,870
996
13

hnRNP G
17,601
1,364
13

PACS1
20,636
1,599
13

BIK
17,348
1,347
13

Glycerol 3 Phosphate
30,027
2,331
13

Dehydrogenase

Olfactomedin-2
14,050
1,091
13

GFR alpha-2
19,167
1,489
13

MSH6
24,882
1,938
13

ANGPTL4
11,861
926
13

Prouroguanylin
32,028
2,501
13

PHAP1
27,112
2,118
13

FKBP25
20,104
1,572
13

BMP-8
22,135
1,733
13

CFHR 1
18,843
1,476
13

Osteocalcin
13,329
1,044
13

HBZ
18,451
1,447
13

HOXD11
22,083
1,733
13

LEDGF
22,979
1,805
13

NeuroD1
12,350
971
13

RanGAP1
19,746
1,552
13

NF-M
21,326
1,677
13

SOX17
15,311
1,204
13

PYY
20,286
1,598
13

IL-20
20,679
1,629
13

Cytochrome c
18,900
1,491
13

IL-15
27,903
2,205
13

CA 15-3
19,348
1,529
13

Hemoglobin
15,999
1,265
13

DCBLD2
12,855
1,017
13

Serpin I1
10,904
864
13

DLL1
14,354
1,137
13

FGF-21
12,809
1,016
13

RNASE6
14,716
1,168
13

Annexin A7
11,296
897
13

PCCA
35,047
2,787
13

GLIPR2
25,308
2,018
13

Desmuslin
29,335
2,343
13

C9
20,378
1,628
13

Proteasome 20S b7
26,068
2,084
13

ARX
11,876
950
12

LIF R alpha
14,718
1,178
12

C1s
35,810
2,870
12

Chymase
13,436
1,078
12

Prion protein PrP/PRNP
25,503
2,047
12

IFN-gamma
21,005
1,686
12

CNOT1
18,773
1,513
12

UROD
9,863
796
12

IL-1 R6/IL-1 Rrp2
17,839
1,441
12

PER1
26,283
2,124
12

CFHR2
14,126
1,143
12

Thymidine Kinase-1
22,402
1,814
12

PTP gamma
17,115
1,387
12

LBP
11,208
910
12

BCAM
21,449
1,743
12

NM23-H1/H2
11,865
965
12

Lysozyme
21,909
1,785
12

Frizzled-5
13,106
1,068
12

PARC/CCL18
22,168
1,808
12

ROR1
17,770
1,451
12

Serpin A8
13,335
1,089
12

Persephin
16,031
1,309
12

IL-13 R alpha 1
23,204
1,897
12

IGFBP-3
20,671
1,690
12

Neurturin
15,921
1,302
12

perilipin 3
27,977
2,288
12

PSMB5
28,746
2,353
12

PLUNC
15,583
1,278
12

Cathepsin G
11,916
978
12

Siglec-9
19,524
1,603
12

MMP-15
20,236
1,663
12

Frizzled-7
14,450
1,188
12

ARB1
16,372
1,346
12

CL-P1
22,520
1,855
12

Glypican 3
9,888
815
12

MFG-E8
17,371
1,431
12

GATA-3
13,033
1,074
12

Frizzled-6
12,262
1,012
12

beta B1 Crystallin/CRYBB1
30,557
2,523
12

Siglec-5/CD170
19,094
1,578
12

TOPORS
17,006
1,406
12

PIN
24,926
2,062
12

Hemoglobin A1c
24,492
2,026
12

S100A8
13,776
1,140
12

EphB4
11,455
948
12

CLC
28,310
2,348
12

Cystatin A
13,139
1,090
12

Transthyretin
8,359
695
12

GSR
21,738
1,807
12

GAPDH
33,874
2,821
12

Trappin-2
10,521
876
12

Plastin L
32,790
2,732
12

PSMA1
12,406
1,034
12

Cathepsin S
11,811
987
12

IGFBP-5
10,509
879
12

LILRA3
21,136
1,770
12

GITR Ligand/TNFSF18
26,583
2,227
12

KRT31
25,914
2,171
12

KCTD10
11,852
993
12

BTD
35,736
2,995
12

LYVE-1
11,219
942
12

ACE
12,738
1,069
12

ECM-1
26,136
2,195
12

ZNF671
8,853
744
12

FoxP3
11,982
1,007
12

ROBO4
12,349
1,039
12

Cystatin C
17,281
1,455
12

BIRC6
33,912
2,857
12

Vitronectin
16,789
1,415
12

beta-Catenin
10,687
901
12

beta -I Tubulin
19,039
1,606
12

E-Cadherin
15,550
1,313
12

IL-1 sRII
18,520
1,565
12

Plectin
24,920
2,109
12

Spinesin
15,999
1,354
12

Endorepellin
16,550
1,402
12

Glut2
16,138
1,368
12

Insulin R
20,894
1,774
12

Serpin D1
9,910
845
12

Azurocidin
19,931
1,699
12

RPS10
20,711
1,765
12

Catalase
11,833
1,009
12

Glut5
18,755
1,601
12

HAI-2
11,962
1,021
12

FGFR1 alpha
20,102
1,716
12

S100A4
11,037
943
12

ARPC3
31,306
2,675
12

Properdin
23,270
1,989
12

Glyoxalase II
9,950
851
12

Netrin-4
17,000
1,453
12

FABP3
15,508
1,327
12

ZBTB4
11,158
955
12

LIMPII
9,671
828
12

Neuritin
15,303
1,311
12

BMP-3b/GDF-10
10,866
931
12

Vasorin
14,981
1,287
12

Cortactin
12,599
1,084
12

Cystatin D
34,225
2,945
12

Smad 1
10,319
889
12

MCP-4/CCL13
11,857
1,023
12

Syndecan-1
12,293
1,061
12

Osteopontin
12,689
1,098
12

ApoE
11,628
1,009
12

APN
14,701
1,276
12

IFN-alpha/beta R1
12,426
1,079
12

Fas/TNFRSF6
16,250
1,412
12

Erythropoietin
23,681
2,059
12

ApoB100
10,424
907
11

Cathepsin H
18,404
1,602
11

TWEAK/TNFSF12
9,556
832
11

Chordin-Like 1
17,692
1,542
11

Pentraxin3/TSG-14
13,010
1,136
11

AFP
19,423
1,697
11

CD61
14,932
1,305
11

Cathepsin D
13,552
1,185
11

DOT1L
26,325
2,303
11

Desmocollin-2
16,532
1,447
11

URB
7,900
692
11

PRSS3
34,998
3,065
11

MASP3
16,807
1,472
11

ADAMTS-19
17,518
1,535
11

Ephrin B1
32,348
2,839
11

TGF-beta 3
5,519
485
11

ApoH
13,306
1,169
11

ALDH1A1
17,032
1,497
11

Nectin-1
13,476
1,186
11

GFAP
10,095
889
11

KLK-B1
11,245
992
11

Secretogranin V/SCG5
26,389
2,329
11

Peroxiredoxin 3
24,889
2,197
11

EphB6
11,747
1,039
11

MYHC
24,624
2,177
11

NABC1
14,986
1,326
11

PSMD1
28,696
2,542
11

AgRP
25,506
2,263
11

IL-23 R
12,193
1,082
11

Galanin
19,866
1,772
11

PIK3IP1
15,876
1,419
11

IL-1 F10/IL-1HY2
14,933
1,335
11

IL-28A
12,491
1,119
11

SOX4
23,277
2,091
11

ANK
18,919
1,701
11

PON1
12,350
1,112
11

Uromodulin
11,681
1,052
11

PPOX
68,229
6,146
11

Histone H4
16,945
1,527
11

Metallothionein
21,390
1,932
11

FOLR3
25,145
2,271
11

Neurokinin-A
11,453
1,035
11

Protein p65
12,098
1,093
11

IL-33
14,059
1,271
11

HDGF
10,307
932
11

APLP-1
17,989
1,628
11

Frizzled-3
10,860
983
11

PGRP-S
10,093
914
11

SOD4
21,887
1,983
11

SERPINB1
17,880
1,620
11

Tenascin C
9,478
859
11

GMF beta
21,813
1,977
11

Fyn
14,718
1,335
11

HPR
23,855
2,164
11

Neuropilin-2
12,929
1,174
11

Lamin A + C
17,020
1,545
11

ZC3H4-N-t
7,586
689
11

GSTP1
9,959
905
11

PON2
15,027
1,366
11

DCXR
36,583
3,326
11

GRO
19,747
1,796
11

Hornerin
21,824
1,987
11

COX-2
11,446
1,043
11

S100A10
11,005
1,003
11

53BP1
10,818
986
11

PKM2
11,338
1,034
11

S-100b
21,976
2,004
11

Lamin B1
17,999
1,643
11

PZP
13,658
1,247
11

Chitotriosidase
18,483
1,688
11

Osteocrin
13,127
1,200
11

PlGF
14,642
1,340
11

LOK
25,305
2,316
11

ALBUMIN
393,095
35,987
11

SHANK1
10,900
1,000
11

TLR1
10,942
1,004
11

HADHA
20,020
1,837
11

ApoD
12,609
1,159
11

PA2G4
22,780
2,096
11

KIF3B
14,052
1,294
11

Ubiquitin + 1
20,890
1,924
11

TXNRD2
22,225
2,048
11

Eotaxin/CCL11
11,692
1,078
11

HCFC1
9,083
838
11

IL-20 R beta
16,265
1,500
11

Pancreastatin
18,187
1,678
11

FGF-10/KGF-2
24,214
2,238
11

Brevican
32,087
2,967
11

CES1
13,529
1,253
11

TIMP-2
7,625
709
11

MMP-10
17,280
1,612
11

CD30 Ligand/TNFSF8
16,618
1,554
11

GIP
16,022
1,498
11

Kallikrein 10
17,316
1,622
11

Ficolin-3
12,019
1,127
11

HNF-3 alpha/FoxA1
9,474
889
11

Thyroglobulin
19,221
1,806
11

TFPI
9,557
898
11

ICAM-3 (CD50)
8,473
797
11

RPL14
27,715
2,607
11

S100A9
10,524
992
11

CA2
25,433
2,397
11

Hoxb3
25,742
2,427
11

Serpin A9
9,448
891
11

IL-20 R alpha
20,061
1,896
11

TFF1
15,618
1,476
11

Pro-BDNF
12,610
1,193
11

NCAM2
22,340
2,115
11

NPTXR
12,663
1,200
11

Guanylin
23,174
2,196
11

ALP
23,389
2,217
11

TMEFF1/Tomoregulin-1
14,826
1,406
11

PSA-total
14,934
1,417
11

KIAA1468
24,926
2,367
11

IL-7 R alpha
13,163
1,250
11

HSP10
15,512
1,474
11

GASP-2/WFIKKN
14,876
1,414
11

SLPI
16,991
1,616
11

Neogenin
15,240
1,453
10

Cerberus 1
13,329
1,274
10

PSMA7
18,938
1,811
10

Beta Defensin 4
14,037
1,345
10

FIH
16,893
1,621
10

CHC17
11,811
1,134
10

Semenogelin I/SEMG1
12,988
1,248
10

hHR23b
25,816
2,480
10

Proteasome 20S alpha
28,990
2,785
10

Histone H3.3
12,968
1,246
10

SOST
12,665
1,218
10

EV15L
18,278
1,759
10

Fetuin A
15,796
1,521
10

Fetuin B
14,710
1,419
10

GULP1/CED-6
8,837
853
10

WIF-1
8,303
802
10

GDF3
22,278
2,152
10

INSL3
14,768
1,428
10

APC
19,874
1,922
10

TSLP
10,278
994
10

ROCK1
26,088
2,527
10

TRA-1-60
20,295
1,967
10

HOXA10
11,787
1,143
10

MYH7
30,234
2,934
10

ACLY
26,989
2,624
10

EVC2
32,549
3,168
10

CTGF/CCN2
15,131
1,473
10

TRA-1-81
20,176
1,965
10

14-3-3 sigma
11,410
1,111
10

NELL2
19,975
1,945
10

Ferritin
17,436
1,700
10

Cytochrome C
13,682
1,336
10

B3GNT2
34,350
3,368
10

Fibrinopeptide A
17,802
1,746
10

PISD
29,273
2,873
10

SAMSN1
9,699
952
10

Glut3
23,318
2,289
10

HSP40
11,379
1,118
10

PD-1
9,723
956
10

PDGF R beta
21,814
2,145
10

SNCG
13,038
1,283
10

ROCK2
10,959
1,079
10

CRTH-2
13,486
1,329
10

MP1
13,087
1,291
10

CD200
10,717
1,058
10

PDIA6
48,676
4,808
10

Grb2
9,662
955
10

CNTF R alpha
23,160
2,290
10

F11
23,087
2,286
10

Frizzled-1
10,409
1,033
10

BMP-9
11,732
1,166
10

ROR2
12,403
1,234
10

L-Selectin (CD62L)
18,250
1,816
10

Clusterin
28,326
2,820
10

AKR1C3
13,212
1,317
10

NCAM-1/CD56
12,556
1,252
10

S100P
7,571
757
10

COMP
17,210
1,721
10

FGFR1
24,579
2,461
10

PARK7
11,114
1,116
10

Laminin 2 alpha
28,122
2,824
10

PI 3-Kinase C2 beta
16,361
1,645
10

IRE1
19,601
1,971
10

Filamin B
28,758
2,892
10

NT5C3
16,181
1,628
10

Lumican
12,928
1,302
10

FGFR2
11,606
1,169
10

AIF
10,471
1,055
10

IL-34
12,580
1,268
10

Multimerin 2
27,651
2,788
10

Latent TGF beta bp2
16,485
1,665
10

ADM
20,656
2,089
10

Inhibin beta
36,341
3,680
10

FOLR1
13,583
1,377
10

SET
16,836
1,708
10

Progranulin
11,457
1,165
10

RELM alpha
13,733
1,399
10

Endothelin Receptor A
25,402
2,588
10

FABP4
10,780
1,102
10

PPP2R5C
18,026
1,849
10

ApoE3
10,881
1,117
10

MN1
25,457
2,618
10

RPS12
19,459
2,002
10

MLCK
24,528
2,535
10

INSRR
12,952
1,340
10

14-3-3 epsilon
9,547
988
10

HP1BP3
20,081
2,079
10

Perilipin-1
24,670
2,555
10

Furin
12,443
1,289
10

ABL1
14,878
1,541
10

Mannosidase II
26,978
2,796
10

IL-17E
16,876
1,751
10

Grainyhead-like protein 1
13,556
1,407
10

homolog/GRHL1

Neurotrimin
16,955
1,759
10

CLIC1
25,403
2,636
10

LOXL1
22,311
2,321
10

14-3-3 theta
10,852
1,130
10

RhoGDI
17,744
1,851
10

ACTH
16,988
1,776
10

Afamin
8,612
901
10

FBPase 1
11,548
1,209
10

Plasminogen
10,100
1,058
10

Kallikrein 11
12,470
1,306
10

Desmoglein-1
14,365
1,505
10

Myoglobin
11,762
1,232
10

Contactin-4
23,432
2,458
10

PECAM-1/CD31
9,641
1,012
10

ADH1C
29,910
3,143
10

ATP5O
35,641
3,745
10

NOV/CCN3
8,775
925
9

CRTAM
14,936
1,575
9

Serpin B3/SCCA1
6,547
691
9

MBL
10,337
1,092
9

CA 125
20,079
2,123
9

Smad 7
11,775
1,250
9

Growth Hormone (GH)
19,096
2,028
9

OX40
13,382
1,421
9

Serpin A5
14,822
1,575
9

TRP-1
7,105
755
9

PEPSINOGEN II
10,821
1,151
9

PEBP4
27,601
2,937
9

mTOR
17,890
1,904
9

hnRNP L
27,909
2,975
9

TACE
6,946
743
9

14-3-3 eta
9,736
1,042
9

IL-17C
9,667
1,035
9

MMP-7
7,507
804
9

Kallikrein 7
11,843
1,269
9

AFG3L2
26,067
2,795
9

VEGI/TNFSF15
8,610
923
9

APP
14,183
1,521
9

LAIR1
12,318
1,321
9

Ran
16,300
1,750
9

Kallikrein 14
9,265
997
9

HSP90
14,336
1,542
9

Nesfatin
14,048
1,512
9

p27
13,818
1,489
9

TIM-1
9,656
1,041
9

Pancreatic Polypeptide
17,427
1,879
9

MYO5A
30,334
3,277
9

CPNE3
34,289
3,706
9

Peroxiredoxin 2
9,101
985
9

Nebulin
27,898
3,020
9

Aldehyde Oxidase 1/AOX1
10,993
1,190
9

BAZ2B
30,281
3,280
9

Actinin alpha 1
11,273
1,222
9

CA3
34,206
3,720
9

CCT3
42,119
4,581
9

MMR
15,277
1,666
9

Progesterone
13,727
1,498
9

HMGB2
24,511
2,680
9

PDX-1
11,126
1,217
9

Gastrokine 1
11,923
1,305
9

Factor XIII
24,822
2,720
9

TGF-beta 2
8,701
956
9

MMP-12
14,227
1,567
9

Caspase-8
21,352
2,355
9

PSMC3
18,155
2,003
9

ITM2B
10,106
1,119
9

PDLIM1
19,468
2,155
9

Plexin B1
8,623
955
9

H6PD
18,509
2,053
9

IL-12 p70
12,656
1,405
9

NAP1L1
30,042
3,338
9

NPM1
9,222
1,025
9

LRP 4
17,002
1,893
9

Prostasin
10,235
1,141
9

p21
20,176
2,249
9

SART1
8,487
949
9

SEZ6L2
6,829
763
9

VSIG4
6,627
742
9

SEMA3A
11,888
1,334
9

Hemoglobin subunit gamma
14,319
1,609
9

2/HBG2

IL-13
21,063
2,367
9

ANGPTL6
19,750
2,220
9

NR3C3
16,064
1,807
9

PEDF
12,963
1,461
9

Livin
11,439
1,294
9

ABI3BP
23,308
2,640
9

Noelin
14,079
1,597
9

HTRA1
13,158
1,493
9

FABP5
12,634
1,435
9

Kremen-2
14,667
1,666
9

SCGF
11,582
1,316
9

RPS3
10,927
1,242
9

B4GalT1
12,904
1,467
9

ACK1
20,317
2,316
9

APOA1BP
29,482
3,367
9

ADAMTS-1
9,085
1,039
9

THOP1
8,529
977
9

IL-7
20,807
2,390
9

TSH
17,891
2,057
9

CLIP170-N-t
32,694
3,770
9

EphA3
17,096
1,977
9

IL-24
26,020
3,011
9

Ntn1
18,855
2,187
9

Fibrinogen gamma chain/FGG
16,767
1,946
9

Rab7a
7,376
859
9

SIM2
23,540
2,740
9

Neuropeptide B
27,884
3,248
9

HCR/CRAM-A/B
25,565
2,978
9

Serpin A12
10,345
1,206
9

OCT3/4
10,070
1,175
9

FER
35,277
4,119
9

ITIH3
7,889
922
9

LIN41
10,096
1,181
9

Mer
10,518
1,235
9

Hepassocin
18,043
2,119
9

PSMD9
13,929
1,637
9

hnRNP A1
10,191
1,200
8

BCHE
18,257
2,157
8

Omentin
13,372
1,583
8

SF20
6,404
760
8

IRS2
31,156
3,700
8

URB2
36,414
4,325
8

GPX3
11,319
1,345
8

MMP-16/MT3-MMP
11,312
1,345
8

GCLC
29,319
3,491
8

Cytokeratin 18
11,134
1,326
8

FH
13,067
1,560
8

IL-17RC
22,955
2,742
8

FGF-5
21,876
2,618
8

GFR alpha-3
20,966
2,514
8

GDI2
29,794
3,574
8

Lamin B2
26,055
3,126
8

ELAVL1
25,752
3,091
8

UGGT
10,288
1,235
8

IL-17R
23,688
2,847
8

CTACK/CCL27
17,666
2,127
8

DBI
10,547
1,278
8

KRTDAP
19,460
2,358
8

SAA
15,444
1,872
8

MYH2
30,261
3,670
8

CRTAC1
20,741
2,517
8

HEG1
17,178
2,085
8

Annexin A2
15,247
1,852
8

P-selectin
18,794
2,289
8

PAI-1
14,386
1,754
8

Factor XIII B
10,474
1,279
8

Advillin-N-t
26,785
3,272
8

Destrin
35,838
4,380
8

LUZP1
27,499
3,371
8

Serpin A10/ZPI
6,054
743
8

HSP32
9,879
1,214
8

Kallikrein 5
13,551
1,669
8

OIT3
25,744
3,187
8

Dkk-1
14,974
1,857
8

KRTHA3B
29,821
3,697
8

ENO1 + ENO2 + ENO3
35,176
4,365
8

Endocan
9,302
1,155
8

MSHa
16,052
1,995
8

AKR1B1
16,054
1,995
8

TXK
19,646
2,443
8

Pro-Cathepsin B
8,992
1,119
8

SOX2
12,143
1,513
8

JAM-A
8,059
1,004
8

SERTAD2
8,481
1,058
8

BMP-7
19,236
2,404
8

SPINK1
10,560
1,321
8

CLIC4
33,130
4,145
8

Human Agrin
22,863
2,863
8

Aldolase A
31,884
4,008
8

UNC5H4
5,974
752
8

GLP-1
16,891
2,127
8

ERRa
10,066
1,268
8

EphB2
14,119
1,780
8

C5b-9
19,517
2,461
8

RNA Polymerase II/POLR2A
6,750
851
8

ASPH
18,420
2,323
8

ANP
23,818
3,005
8

Antithrombin III
37,705
4,765
8

Cytokeratin 14
14,098
1,785
8

PYK2
13,820
1,750
8

GRP
19,342
2,451
8

AHNAK
22,341
2,833
8

hCG alpha
18,589
2,361
8

SorLA
5,910
751
8

EFTUD2
33,177
4,216
8

Endorphin Beta
15,399
1,961
8

Cytokeratin 17
33,004
4,210
8

USP5
18,828
2,402
8

Granzyme A
9,694
1,239
8

CA 9
10,917
1,396
8

QPRT
16,202
2,073
8

JARID2
8,814
1,128
8

S100A1
6,426
823
8

ADAMTS-L2
11,550
1,481
8

Pleckstrin
8,101
1,039
8

RELT/TNFRSF19L
15,791
2,026
8

IBP160
28,730
3,689
8

nNOS
6,642
853
8

GADD45A
22,586
2,906
8

C-peptide
18,982
2,443
8

Moesin
25,077
3,230
8

Hepcidin
14,873
1,917
8

CCR1
12,865
1,660
8

Pro-MMP-7
9,106
1,178
8

CLEC3B
18,624
2,409
8

Bax
15,303
1,988
8

HSP60
11,180
1,455
8

PARVB
31,655
4,124
8

HAI-1
10,994
1,434
8

FoxO1
9,442
1,233
8

SOD1
8,497
1,111
8

APCS
14,920
1,952
8

Desmoglein-2
10,269
1,345
8

ProSAAS
15,134
1,983
8

ALDH9A1
27,565
3,613
8

EphA4
20,368
2,670
8

C4.4A
10,539
1,392
8

Corneodesmosin
18,481
2,445
8

MICB
9,586
1,269
8

HPD
22,401
2,967
8

CAD
31,643
4,193
8

HSPA8
9,705
1,289
8

RPS20
12,675
1,684
8

Serpin A7
6,137
816
8

TNK1
19,330
2,569
8

IDUA
16,868
2,242
8

SHP-1
6,067
809
8

FGF-11
19,712
2,632
7

Serpin A11
5,985
800
7

TWF2
5,194
694
7

SSEA-1
8,759
1,172
7

Proteasome subunit beta type
30,204
4,044
7

2/PSB2

FLG2
28,128
3,772
7

MIP-1d
9,655
1,297
7

p53
13,609
1,828
7

Kallikrein 6
10,949
1,477
7

SHBG
14,801
1,997
7

Hemopexin
10,666
1,440
7

GRP
19,335
2,611
7

PTN
8,435
1,140
7

DEFA6
32,020
4,333
7

Talin1
6,246
846
7

NASP
27,949
3,786
7

MIP 2
18,758
2,544
7

EIF3S2
20,875
2,838
7

VCP
6,570
895
7

Chem R23
10,869
1,481
7

Ceruloplasmin
23,796
3,244
7

TFF3
9,185
1,252
7

HN1
19,340
2,647
7

ITIH2
6,350
871
7

APJ
10,173
1,395
7

HPRT
14,540
2,001
7

RYK
12,827
1,766
7

EN2
24,726
3,414
7

ETL
30,804
4,258
7

TRKB
14,269
1,976
7

GM2A
33,324
4,617
7

KRT82
20,796
2,887
7

ERp29
30,253
4,203
7

MMP-13
10,277
1,429
7

ATPB
27,655
3,848
7

Cardiotrophin-1/CT-1
8,538
1,192
7

CBP
18,072
2,524
7

ZC3H8
7,211
1,009
7

Presenilin 2
9,385
1,313
7

CALML5
28,528
3,994
7

Cystatin B
15,694
2,199
7

AR (Amphiregulin)
10,446
1,465
7

Presenilin 1
13,067
1,833
7

SART3
10,756
1,511
7

S100A7
8,422
1,183
7

Laminin gamma 1
29,790
4,187
7

LPS
11,742
1,651
7

MANF
7,721
1,086
7

ASH2L
31,342
4,418
7

GLRX1
10,292
1,452
7

NRG3
25,315
3,582
7

LH
13,511
1,916
7

ENSA
28,511
4,045
7

FRY
24,131
3,424
7

DDX3Y
23,860
3,386
7

GNB1
26,383
3,746
7

Proteasome 20S alpha 5
21,606
3,070
7

NF1
20,770
2,954
7

Proteasome 26S S5
9,597
1,365
7

TRPM7
9,005
1,281
7

Oxytocin-neurophysin 1/OXT
15,985
2,280
7

C1RL
33,839
4,831
7

Thymosin b10
7,114
1,017
7

BPIFB1
25,654
3,666
7

VIP Receptor 2
11,093
1,588
7

MFAP4
26,647
3,826
7

Fibrillin 1
13,029
1,872
7

Desmin
7,344
1,056
7

PAK7
8,754
1,260
7

CD27/TNFRSF7
13,913
2,005
7

Integrin alpha V
10,766
1,553
7

HRSP12
9,883
1,426
7

14-3-3 zeta
11,343
1,641
7

SAA4a
6,313
914
7

Syndecan-3
9,997
1,448
7

Cezanne
29,907
4,336
7

PEPSINOGEN I
7,920
1,149
7

PPARg2
12,649
1,836
7

LTBP4
27,354
3,987
7

GATM - C-terminal
27,891
4,067
7

IL-17D
12,239
1,785
7

IL-12 p40
8,963
1,308
7

TPA
9,924
1,448
7

SOD-3
5,873
857
7

Serpin B6
7,301
1,068
7

Legumain
13,774
2,020
7

OBCAM
7,412
1,087
7

MCP-2
9,181
1,347
7

CA 19-9
18,939
2,790
7

IL-10 R beta
8,858
1,308
7

Procalcitonin
11,925
1,763
7

Thrombin
9,030
1,338
7

IL-1 F7/FIL1 zeta
19,728
2,922
7

EHD3
28,988
4,314
7

Gelsolin
13,443
2,002
7

Calbindin D
8,301
1,238
7

FCGBP
23,372
3,486
7

CHORDC1
34,738
5,182
7

gamma Catenin
35,040
5,229
7

BACE-1
7,911
1,184
7

Calreticulin
9,708
1,453
7

EphA8
13,606
2,038
7

Granzyme M
26,422
3,977
7

Thrombospondin-2
9,902
1,491
7

Wilms Tumor 1
11,351
1,713
7

FOXN3
20,571
3,105
7

SPEN
9,143
1,381
7

VDUP-1
11,347
1,715
7

POMC
12,842
1,942
7

Tyk2
12,720
1,924
7

C6 -N-t
31,458
4,763
7

PDE1B
38,835
5,883
7

TAB182
6,300
955
7

IL-16
8,799
1,335
7

Rbm15
8,192
1,244
7

Cytokeratin 19
14,290
2,178
7

SOD2
5,893
898
7

Eosinophil derived
41,850
6,384
7

neurotoxin/EDN

Pro-MMP-9
11,329
1,731
7

Lubricin
28,213
4,317
7

GMNN
15,403
2,357
7

67LR
27,082
4,151
7

TRPS1
5,284
811
7

Dopamine beta Hydroxylase/DBH
31,998
4,911
7

ITGB4BP
14,950
2,297
7

hnRNP U
17,186
2,643
7

IDH1
7,095
1,092
7

SynCAM
5,281
813
7

KIAA1967
24,888
3,829
6

CEA
12,459
1,930
6

Resistin
10,650
1,650
6

Syntaxin 7
6,052
942
6

NET1
14,069
2,194
6

CS
29,999
4,681
6

COL19A1
32,995
5,150
6

EphB1
15,822
2,471
6

EPPK1
20,109
3,142
6

C9orf40
44,210
6,911
6

LOX
27,305
4,271
6

Lymphotoxin beta R/TNFRSF3
9,071
1,421
6

Neuropeptide Y
13,823
2,170
6

p39
15,911
2,503
6

DDT
12,641
1,991
6

MCMP2
6,641
1,050
6

GNPTG
29,877
4,727
6

Angiopoietin-like 2
11,963
1,895
6

CIP29
19,262
3,070
6

TOP2B
6,184
986
6

Corticosteroid-binding globulin
28,310
4,518
6

non-muscle Myosin IIA/Myosin
17,195
2,747
6

BAFF
8,887
1,420
6

C2
17,347
2,774
6

Plxdc2
14,314
2,293
6

FUCA2
14,367
2,307
6

Ube2L3
7,345
1,180
6

DMRN9
20,206
3,246
6

CARHSP1
17,206
2,767
6

GDF9
16,088
2,597
6

SMAC
9,532
1,539
6

MAGP-2
10,786
1,742
6

CYTL1
22,614
3,666
6

GARNL1
34,998
5,680
6

EMSY
13,832
2,248
6

BMPR-IB/ALK-6
11,233
1,828
6

PCNA
8,094
1,319
6

Apex1
11,577
1,888
6

LAMP1
8,127
1,328
6

Filamin A
19,524
3,192
6

pro-Glucagon
12,363
2,021
6

VEGF R1
8,768
1,434
6

Beta 2M
15,913
2,603
6

IL-10 R alpha
12,254
2,007
6

ROS
9,181
1,508
6

HE4
10,852
1,785
6

ZDHHC18
6,742
1,110
6

ALK
17,158
2,828
6

CLPS
35,213
5,809
6

RPL17
5,916
979
6

Proteasome subunit beta type
21,023
3,482
6

4/PSB4

Ubiquitin
7,605
1,263
6

LCMT2
13,775
2,290
6

Versican isoform V0
5,391
897
6

hnRNP A2B1
6,865
1,142
6

Envoplakin
29,028
4,837
6

GPCR GPR116
24,956
4,167
6

LTK
12,381
2,077
6

Vasopressin
10,608
1,782
6

Vitamin D Receptor
7,490
1,261
6

SDF4
5,342
903
6

TRPC1
8,755
1,486
6

CA150
25,973
4,431
6

COTL1
36,104
6,178
6

HMGN2
13,897
2,383
6

NAPRT1
26,591
4,561
6

hGH
10,223
1,755
6

SMA
7,741
1,331
6

Glutamyl hydrolase gamma/CGH
27,350
4,730
6

CCL14/HCC-1/HCC-3
14,063
2,437
6

GRHPR
30,827
5,343
6

Prosaposin
25,314
4,389
6

COLEC10
32,916
5,716
6

TROPONIN I
8,726
1,518
6

MDH2
31,056
5,402
6

PSP
8,033
1,398
6

Ghrelin
14,501
2,536
6

MTUS1
11,090
1,946
6

Netrin G2
13,883
2,440
6

ALS
30,187
5,306
6

Notch-2 ICD
6,616
1,166
6

FBP 38
23,760
4,197
6

FAK
12,914
2,287
6

Intergrin a6
6,580
1,169
6

DAN
6,687
1,191
6

BLC/BCA-1/CXCL13
22,344
3,987
6

Troponin C
16,335
2,924
6

PF4V1
6,813
1,220
6

G3BP
27,679
4,971
6

ADAMDEC1
38,263
6,875
6

CCDC126
38,542
6,933
6

ACACA
12,477
2,246
6

EphA5
17,306
3,129
6

Hck
27,551
4,990
6

NRG2
20,529
3,721
6

hnRNP C1 + C2
15,767
2,863
6

MYL3
16,977
3,084
6

Peroxiredoxin 5
8,702
1,585
5

Vitamin K-dependent protein S
11,877
2,166
5

PTK 7
6,270
1,146
5

UQCRH
6,473
1,187
5

SYK
9,040
1,660
5

CART
11,458
2,105
5

Serpin A4
10,983
2,020
5

TXNDC4
5,396
993
5

Apo (a)
26,621
4,897
5

APM2
23,123
4,267
5

ITGB5
7,511
1,387
5

14-3-3 gamma
21,592
3,992
5

Dermcidin
32,907
6,087
5

AKR7A2
22,592
4,183
5

ORP150
43,150
7,991
5

VWF
11,616
2,159
5

Cytokeratin 4
34,318
6,379
5

GPI
10,744
1,999
5

CCDC25
12,241
2,287
5

MIP-1b
21,425
4,003
5

Midkine
10,492
3,966
5

DSPG3
10,258
1,924
5

AKAP9
23,873
4,479
5

BAD
28,643
5,383
5

Apolipoprotein L 2
20,390
3,838
5

LMW-PTP/ACP1
6,299
1,187
5

EFEMP2
34,688
6,544
5

HTRA2
11,121
2,106
5

Kallikrein 8
7,563
1,434
5

KLF4
8,885
1,695
5

EMILIN1
20,810
3,977
5

XEDAR
13,419
2,566
5

Aconitase 1
36,013
6,906
5

CHI3L1
14,823
2,844
5

hCGb
13,698
2,632
5

DARS2
20,993
4,055
5

UPB1
5,689
1,099
5

ERp72
33,016
6,381
5

HIP1R
14,640
2,832
5

BD-1
31,963
6,213
5

Ctip2
32,968
6,411
5

D4 GDI
35,486
6,902
5

CCK
11,685
2,275
5

PCPE-1
7,362
1,435
5

CRP
12,296
2,398
5

Cux2
30,730
5,993
5

MAGI2
6,121
1,195
5

MyBPC3
7,566
1,481
5

ARP2/3
32,580
6,412
5

EEF2
28,328
5,578
5

Kallikrein 2
12,048
2,376
5

Tryptophanyl
6,318
1,246
5

LTA4H
6,633
1,308
5

PGAM1
11,278
2,225
5

PSMA2
6,312
1,250
5

alpha 1,2 Mannosidase
24,257
4,805
5

IA/MAN1A1

Cytokeratin 16
31,201
6,214
5

SRMS
13,275
2,644
5

GDA
10,897
2,179
5

C3orf75
30,816
6,165
5

FASTKD5
22,699
4,543
5

CETP
10,711
2,147
5

DPP3
26,870
5,391
5

ARFGEF3
27,311
5,495
5

Calpain 1
30,366
6,110
5

Csk
14,867
3,010
5

Cytokeratin 15
15,647
3,170
5

DEFA1/3
10,344
2,102
5

Nucleobindin 1/NUCB1
7,302
1,487
5

Factor XII
22,247
4,543
5

ENO1
33,840
6,948
5

BRSK1
34,652
7,193
5

fast skeletal Myosin
25,640
5,324
5

Factor V
19,277
4,008
5

ASXL1
36,962
7,702
5

mGLUR5
6,658
1,391
5

Cytokeratin 10
31,077
6,498
5

ESR1
14,873
3,114
5

beta III Tubulin/CUBB3
30,266
6,360
5

LDHB
9,176
1,935
5

TRPC6
7,283
1,538
5

Serotonin
9,128
1,932
5

p23
17,449
3,697
5

CPA1
12,799
2,725
5

Ahsp
31,108
6,630
5

Kilon
6,974
1,487
5

Protein Z
9,006
1,924
5

Calpastatin
14,611
3,123
5

BIN2
32,472
6,951
5

EphB3
29,870
6,398
5

MFI2
6,428
1,380
5

Cytokeratin 3
30,988
6,656
5

EPHX2
18,886
4,066
5

Cytokeratin 5
30,686
6,633
5

PCAF
15,372
3,331
5

ASK1
32,379
7,036
5

CLTA
30,607
6,675
5

CNDP1
11,231
2,453
5

MPCA
6,778
1,481
5

Mimecan
9,143
1,998
5

HSC70
7,026
1,536
5

Fumarylacetoacetate
10,349
2,263
5

hydrolase/FAH

GHRF
13,863
3,033
5

ADH1B
30,832
6,758
5

ITIH1
9,129
2,006
5

DNER
15,966
3,513
5

MBP
6,419
1,419
5

Apelin
15,048
3,328
5

LYPA1
17,405
3,861
5

CACNB4
11,336
2,516
5

BPGM
37,917
8,508
4

Cadherin 22
23,589
5,300
4

HIBADH
14,795
3,332
4

VGF
8,374
1,891
4

ABAT
33,350
7,579
4

G0/G1switch 2
24,528
5,586
4

Ephrin B2
12,903
2,939
4

SCG3
6,856
1,563
4

ERAB
27,030
6,165
4

CHREBP
49,341
11,274
4

Hemoglobin subunit delta/HBD
15,276
3,496
4

C1qTNF1
10,183
2,332
4

Haptoglobin
25,036
5,735
4

D-Dimer
22,417
5,135
4

Calmodulin
25,018
5,735
4

EphA7
20,756
4,759
4

alpha Tubulin
25,139
5,767
4

PRSS23
28,200
6,493
4

Cytokeratin 20
35,636
8,215
4

Tec
8,887
2,056
4

Coronin 3
18,867
4,368
4

TIM-4
6,159
1,431
4

CD 163
22,691
5,284
4

MGP
4,905
1,159
4

Aspartate Aminotransferase/AST
30,603
7,280
4

MYH6
7,894
1,879
4

Karyopherin beta 1
7,061
1,685
4

DR3/TNFRSF25
8,186
1,955
4

CECR1
17,760
4,255
4

ACTBL2
32,611
7,816
4

CNN2
32,734
7,851
4

BMPR-IA/ALK-3
8,288
2,003
4

BMP-4
16,296
3,954
4

GDI1
30,857
7,512
4

TYRO10
17,386
4,242
4

TAF4
4,514
1,105
4

hnRNP M1-M4
30,864
7,596
4

ZAP70
13,752
3,393
4

Stathmin 1
7,220
1,797
4

HLA-C
20,846
5,197
4

Argininosuccinate Lyase/ASL
20,255
5,052
4

Integrin beta 6
6,793
1,695
4

TRF 2
6,789
1,698
4

Chromogranin C
33,216
8,359
4

CLEC14A
18,246
4,600
4

ENPP2
20,082
5,066
4

Itk
22,803
5,775
4

MCM
4,756
1,206
4

Bcl-w
14,284
3,625
4

PI 3Kinase p85 beta
17,592
4,477
4

PTPRD
14,394
3,667
4

LEKTI/SPINK5
6,175
1,582
4

Lyn
14,424
3,703
4

Fen 1
12,232
3,143
4

Factor IX
10,434
2,690
4

CRMP2
32,732
8,486
4

EPB41
20,157
5,294
4

MINA
20,296
5,347
4

PCBP1
6,569
1,731
4

Lck
14,313
3,795
4

KHSRP
23,444
6,216
4

DAK
20,065
5,326
4

IL-1 R4/ST2
7,423
1,985
4

Histone H2A.Z
11,165
2,985
4

ESD
28,989
7,860
4

CO4A2
23,998
6,563
4

ZAG
13,214
3,629
4

C8G
38,929
10,740
4

HABP2
8,976
2,489
4

Histone H1.2
12,303
3,442
4

ACAA2
29,429
8,253
4

Cytokeratin 13
29,943
8,407
4

Bassoon
26,516
7,480
4

Alpha 1 Microglobulin
8,964
2,531
4

COL9A3
29,929
8,451
4

BAF57
8,681
2,456
4

PTH
12,981
3,684
4

ART3
31,673
9,030
4

ADAMTS-4
20,840
6,073
3

EEF1G
31,761
9,274
3

Androgen Receptor
15,275
4,504
3

MATK
19,069
5,658
3

KCC3
7,749
2,301
3

Eps 15
21,734
6,459
3

Non-muscle Actin/Actin
5,608
1,688
3

Chromogranin A
10,162
3,063
3

GST
11,951
3,608
3

FBP2
27,047
8,250
3

BID
16,213
4,999
3

MMP-19
9,345
2,921
3

MDH1
31,448
9,851
3

Selenoprotein P
12,514
3,929
3

Arp2
28,472
8,970
3

KMT2B
19,797
6,293
3

CPS1
29,253
9,391
3

Calretinin
15,726
5,049
3

Apolipoprotein F
31,493
10,152
3

ACAA1
53,682
17,313
3

HSP27
28,256
9,263
3

CEP57
41,348
13,618
3

IGFBP-1
28,402
9,409
3

PCMT1
7,839
2,600
3

BPIL1
27,615
9,174
3

eIF4A1-N-t
28,241
9,390
3

Alpha Lactalbumin
24,829
8,276
3

PDGF R alpha
10,413
3,483
3

CENPF
45,200
15,231
3

Creatine Kinase MM/CKMM
15,837
5,352
3

Asialoglycoprotein Receptor
34,453
11,677
3

2/ASGR2

Phosphoserine
7,504
2,555
3

Aminotransferase/PSAT1

Gastrin
15,286
5,209
3

Aldolase C
30,554
10,440
3

CAPZA1
33,615
11,534
3

IDH3A
11,628
3,991
3

Keratin 38
28,863
10,019
3

GOT2
19,183
6,788
3

Alpha Fodrin
48,914
17,520
3

GLUD1
28,145
10,127
3

D6
93,749
33,817
3

GBE1
16,346
5,928
3

Krt73
26,375
9,621
3

E1 Ubiquitin Activating
31,440
11,579
3

Enzyme/UBA1

BCOR
29,629
10,925
3

CPN1
37,920
13,989
3

PTEN
7,858
2,919
3

Cathelicidin
52,356
19,480
3

GPLD1
11,925
4,497
3

MCM5
8,415
3,174
3

NQO2
26,040
9,966
3

GCDFP 15
17,450
6,716
3

RET
12,212
4,718
3

A1BG
21,781
8,423
3

HEXA
6,928
2,685
3

Acetyl-CoA
36,534
14,302
3

acetyltransferase/ACAA

Glucosidase 2 subunit
25,405
9,958
3

beta/PRKCSH

KRT72
7,297
2,910
3

KIF5B
21,407
8,540
3

PPP2R1B
39,140
15,649
3

gamma-Thrombin
4,713
1,886
2

Alcohol Dehydrogenase/ADH
24,554
9,882
2

EHD1
19,101
7,828
2

COPS8
35,389
14,607
2

FRK
16,299
6,772
2

IGF2BP2
14,289
6,058
2

alpha Glucosidase II
27,129
11,668
2

KSR1
25,990
11,270
2

CPN2
27,165
11,812
2

LAG-3
9,531
4,216
2

AK2
28,573
12,715
2

PEPD
31,127
13,886
2

ADAS
39,014
17,785
2

Creatinine
8,593
3,935
2

COL4A3
60,917
27,992
2

LMAN2
7,032
3,237
2

RIP1
5,730
2,655
2

Cytokeratin 9
29,530
13,696
2

SPARCL1
10,411
4,868
2

Filamin C
22,129
10,356
2

MIP-3 beta
12,465
5,876
2

KRT85 - N-terminal
8,000
3,771
2

LAD
26,771
12,673
2

GOLPH4
20,468
9,730
2

Cytochrome b5
34,127
16,283
2

ADH4
44,681
21,658
2

ARPC2
37,369
18,137
2

LYRIC
5,750
2,801
2

Angiopoietin-1
35,269
17,338
2

FDPS
45,949
22,810
2

Apolipoprotein L 1
28,753
14,526
2

DPEP2
19,516
10,038
2

Vitamin D-BP
11,041
5,761
2

Ankrd26
19,308
10,115
2

APA
37,339
19,696
2

ArgRS
39,318
20,781
2

Fibrinopeptide B
24,202
12,927
2

LAP3
26,573
14,350
2

Ihh
5,828
3,148
2

ALDH16A1
33,383
18,088
2

IQGAP1
24,104
13,223
2

LASP1
5,886
3,255
2

Integrin b1
12,457
7,147
2

DPPI
19,671
11,340
2

TRAP220
16,448
9,486
2

Glutathione Synthetase/GSS
21,802
12,769
2

BASP1
45,346
27,835
2

Btk
29,078
18,010
2

ATP5A
40,930
26,042
2

Keratin 36
6,707
4,273
2

ECHS1
29,681
18,911
2

Desmocollin 1
37,169
24,297
2

DRIL1
25,260
16,570
2

LTF
14,762
9,845
1

GART
27,356
18,249
1

Contactin-3
30,249
20,237
1

S100 A8/A9
15,811
10,676
1

Arp3
38,823
26,920
1

GOLPH2
36,285
25,479
1

ISOC2
23,216
17,693
1

alpha Actinin 4
31,888
25,074
1

GREMLIN
22,410
17,965
1

Frizzled 8
26,113
21,577
1

LAM b1
55,386
46,638
1

PTHLP
14,764
12,907
1

LAF4
25,113
22,304
1

MMP-20
21,745
21,591
1

CAP1
54,249
57,481
1

Fc gamma RIIIB
18,108
19,332
1

BAI-1
12,679
13,710
1

Glypican 5
16,588
19,328
1

Aspartyl Aminopeptidase/DNPEP
35,637
43,824
1

IQGAP2
30,386
39,526
1

ALAD
34,765
54,447
1

ApoA4
28,211
50,991
1

KIAA0319L
10,004
18,789
1

Calcitonin
5,629
10,804
1

Neurogranin
19,438
75,993
0

HRG-alpha
15,320
278,947
0

	Number	Date	Country
Parent	17085695	Oct 2020	US
Child	17968631		US

MESENCHYMAL STEM CELL COMPOSITIONS AND METHODS OF MAKING

Information

Publication Number

Date Filed

Date Published

Inventors

Original Assignees

CPC

International Classifications

Abstract

Description

Claims

CROSS-REFERENCE TO RELATED APPLICATIONS

Continuation in Parts (1)