Research Project
8314618
DESCRIPTION (provided by applicant): Primorigen Biosciences SBIR Proposal Abstract Primorigen Biosciences will use SBIR funds to develop an advanced cell culturing methodology to increase the efficiency of directed differentiation and to boost functional maturity of induced pluripotent stem cell-derived hepatocytes. The new technology uses proprietary cell culture media additives to recreate native biophysical properties of the cellular microenvironment and encourage cells to secrete and remodel extracellular matrix using their own endogenous machinery to boost progenitor cell proliferation and more complete differentiation to resemble primary hepatocyte function. Phase I studies will determine the optimal parameters for applying the new technology during differentiation and maturation, using established hepatocyte characterization assays to assess the functionality and maturity of the differentiated hepatocytes. Phase II studies will verify and optimize compound metabolism and activity of Phase II enzymes, and adapt the improved hepatocyte differentiation protocol to higher-throughput formats such as 96 and 384 well plates to enable compound screening for drug discovery and toxicity studies. The product will be commercialized globally through Primorigen's direct customer base and major strategic alliance partners. PUBLIC HEALTH RELEVANCE: Primorigen Biosciences, Inc. SBIR Project Narrative There is a worldwide shortage of primary hepatocytes for use in both therapeutic and research applications, including drug discovery and toxicity screening. In addition, the tendency of primary hepatocytes to lose most hepatic functions in a tissue culture environment suggests a great need for a scalable and reproducible source of hepatocyte-like cells of known genotype. While current stem cell culturing methods have been successful and efficient in generating hepatocyte-like cells that mimic several functions of primary liver cells, they have not been successful in producing cells that completely mimic primary cell function, particularly expression of genes encoding for p450 cytochrome enzymes critical for toxicity analysis and key liver functions. The SBIR technology will address this problem using proprietary, patent-pending media additives that enable stem cells to create a more in vivo-like microenvironment using their own endogenous mechanisms to produce a more fully functional stem cell-derived hepatocyte.
