A Chemically Defined Substrate Array to Optimize Hepatocyte Derivation from IPSCs

描述（由申请人提供）：Primorigen将使用SBIR基金开发一种阵列系统，该系统可以识别化学定义的表面，以优化诱导多能干细胞（hiPSC）分化和成熟。该平台最初将验证其帮助提高干细胞衍生肝细胞功能成熟度的能力，特别是细胞色素p450（CYP）活性，随后将验证其用于大规模生产hiPSC衍生肝细胞的能力。尽管人类多能干细胞被广泛认为有希望为许多毁灭性的退行性疾病提供新的疗法，并为更快速、更具成本效益的药物开发提供新的筛选工具，但还没有关于具有足够功能成熟度的细胞用于这些应用的报道。Primorigen的技术将通过开发一种新的肽阵列来评估不溶性细胞信号对干细胞衍生谱系成熟的影响，从而满足这一需求。第一阶段研究将验证阵列的稳定性和识别条件的能力 其改善原代和hiPSC衍生肝细胞的功能和增殖活性。第二阶段将把这种方法应用于其他谱系，包括hPSC衍生的心肌细胞，并适应高容量生产肝细胞的最佳条件。计划的产品包括：1）用于鉴定最佳表面处理的用户友好的阵列试剂盒，以及最终，2）大量产生的功能成熟细胞，以支持药物筛选应用。

DESCRIPTION (provided by applicant): Primorigen will use SBIR SHIFT funds to develop an array system that can identify chemically-defined surfaces to optimize induced pluripotent stem cell (hiPSC) differentiation and maturation. The platform initially will be validated for its capacty to help increase functional maturity of stem cell-derived hepatocytes, particularly cytochrome p450 (CYP) activity, and subsequently for large scale production of hiPSC-derived hepatocytes. Despite the widely acknowledged promise of human pluripotent stem cells to provide new therapies for numerous devastating degenerative diseases and new screening tools for more rapid, cost effective drug development, there are no reports of cells with sufficient functional maturity for these applications. Primorigen's technology will address this need by developing a novel peptide array for assessing the impact of insoluble cell signals on maturation of stem-cell derived lineages. Phase I studies will validate array stability and capacity to identify conditions that improve function and CYP activity of primary and hiPSC-derived hepatocytes. Phase II will apply this approach to other lineages including hPSC-derived cardiomyocytes, and adapt the optimal conditions for high-capacity production of hepatocytes. Planned products include: 1) a user- friendly array kit to identify optimal surface treatments, and ultimately, 2) functionally mature cells produced in large volumes to support drug screening applications.