Research Project
8315667
DESCRIPTION (provided by applicant): Primorigen Biosciences will develop an enhanced cell culturing technology that dramatically increases proliferative and differentiation capabilities of human bone-marrow derived mesenchymal stem cells (hMSC's) for neural induction, and ultimately for induction to other lineages for research and clinical applications. The technology consists of proprietary cell culture media additives that effectively recreate native biophysical properties of the cellular microenvironment and encourage cells to secrete and remodel extracellular matrix (ECM) using their own endogenous machinery. The net effect is to dramatically enhance proliferation and differentiation capacity. Phase I studies will assess feasibility by determining whether the proprietary additives improve expansion and neural induction of hMSCs under prolonged passaging (10+) as measured by biomarker profiling and efficacy after transplant into SCI animal models. Phase II studies will focus on increasing MMC-driven hMSC expansion and extending the Phase I studies to extending the Phase I studies to include induction, transplantation, and testing of hMSCs in additional neurodegenerative disease models, such as amyotrophic lateral sclerosis (ALS) and Parkinson's disease. The new technology will be commercialized globally through Primorigen's own direct network of customers and through its major strategic partners. PUBLIC HEALTH RELEVANCE: The last two decades have seen an overwhelming amount of basic and preclinical research demonstrating the therapeutic promise of human mesenchymal stem cells (hMSCs) for neurodegenerative diseases, spinal cord and brain injuries, cardiovascular diseases, diabetes mellitus, and diseases of the skeleton. In most of these studies, treatment with hMSCs results in substantial functional benefit and these pre-clinical studies have led to the initiation of a number of clinical trials worldwide. To obtain sufficient hMSCs for these autologous clinical applications, the hMSCs must be harvested from the patient and quickly expanded in vitro before transplantation back to the patient. Recent studies suggest that neural induction of hMSCs (NI-hMSCs) prior to transplantation could provide a significant advantage over naive hMSC in treatment of animal models of spinal cord injury (SCI). Furthermore, recent studies by our collaborators reveal that the hMSCs expanded using standard cell culturing conditions lose their ability to generate NI-hMSCs after 4 passages, far short of the estimated expansion required to generate sufficient cell populations for clinical therapy. To address this problem, we have devised a proprietary, patent-pending cell culturing technology to effectively recreate native biophysical properties of the cellular microenvironment that encourages cells to secrete and remodel extracellular matrix (ECM) using their own endogenous machinery as a solution for increasing proliferation rates and maintaining differentiation capacity over a sufficient number of passages to generate the cells needed for therapeutic applications.
