A Chemically Defined Substrate Array to Optimize Hepatocyte Derivation from IPSCs

描述(申请人提供)：Primorigen将利用SBIR Shift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)的分化和成熟。该平台最初将被验证其能力，以帮助提高干细胞来源的肝细胞的功能成熟度，特别是细胞色素P450(CYP)活性，并随后用于大规模生产HiPSC来源的肝细胞。尽管人们普遍认为，人类多能干细胞有望为许多毁灭性的退行性疾病提供新的治疗方法，并为更快、更具成本效益的药物开发提供新的筛选工具，但目前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多肽阵列来满足这一需求，以评估不可溶细胞信号对干细胞来源谱系成熟的影响。第一阶段研究将验证阵列的稳定性和识别条件的能力 改善原代和HiPSC来源的肝细胞的功能和CYP活性。第二阶段将把这种方法应用于其他谱系，包括hPSC来源的心肌细胞，并适应高能力生产肝细胞的最佳条件。计划中的产品包括：1)用户友好的阵列套件，以确定最佳的表面处理，并最终，2)大量生产功能成熟的细胞，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.