A Novel Substrate to Amplify Growth Factor Impact on hPSC Differentiation

Primorigen Biosciences(R)项目摘要Primorigen将利用SBIR基金开发一种改变范式的技术，利用一种新型肽来扩增和定向分化人类多能干细胞（hPSCs），该肽通过放大内源性生长因子的影响并最大限度地减少对外源性生长因子的需求，从而显著降低成本。该肽已被用于放大多种生长因子的生理效应，通过在提案中描述的机制。I期研究将证明多肽在标准聚苯乙烯培养容器上的效用，以增强hipsc在含有低生长因子的无血清培养基中的增殖，并作为一种更经济有效的定向分化的有效剂。我们将

DESCRIPTION (provided by applicant): Primorigen Biosciences(R) Project Abstract Primorigen will use SBIR funds to develop a paradigm-changing technology for expansion and directed differentiation of human pluripotent stem cells (hPSCs) using a novel peptide that dramatically reduces costs by amplifying the impact of endogenous growth factors and minimizing the need for exogenous growth factors. The peptide has been used to amplify the physiological effects of multiple growth factors, through mechanisms described in the proposal. Phase I studies will demonstrate the utility of the peptide on standard polystyrene culture vessels to enhance proliferation of hiPSCs in reduced growth factor-containing serum-free media, and to serve as an effective agent for more cost-efficient directed differentiation. We will demonstrate the latter feasibility by using Primorigen's proprietary, high efficiency hepatocyte differentiation protocol for differentiation of hiPSCs on the peptide-modified surfaces, providing proof of principle for extending the technology to other lineages. Phase II activities will test an validate the peptide for use in 1) scaled-up production of hiPSCs on microcarriers in stirred-cell suspension bioreactors, 2) effective growth-factor dependent differentiation of other lineages in the presence of the peptide, to accompany scale-up. Products developed from this proposal will include the peptide-coated cultureware along with companion, reduced growth factor media for hiPSC maintenance and differentiation into various cell types, beginning with hepatocytes.