A Chemically Defined Substrate Array to Optimize Hepatocyte Derivation from IPSCs

用于优化 IPSC 肝细胞衍生的化学成分确定的基质阵列

• 批准号: 8590641
• 负责人: Jae-Sung Lee
• 金额: $ 19.97万
• 依托单位: PRIMORIGEN BIOSCIENCES, INC.
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-30 至 2015-08-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8590641
• 关键词: Address; Adhesions; Adsorption; Albumins; Animals; Behavior Control; Biomedical Engineering; Cardiac Myocytes; Cell Adhesion; Cell Differentiation process; Cell Line; Cell physiology; Cells; Clinical; Culture Media; Cytochrome P450; Degenerative Disorder; Dependence; Derivation procedure; Drug Metabolic Detoxication; Engraftment; Environment; Enzymes; Evaluation; Excretory function; Exhibits; Extracellular Matrix; Failure; Fostering; Funding; Government; Growth Factor; Hepatocyte; Human; In Vitro; Label; Legal patent; Ligands; Lipids; Metabolism; Modeling; Peptide Library; Peptides; Persons; Pharmaceutical Preparations; Phase; Phenotype; Pluripotent Stem Cells; Population; Preclinical Drug Evaluation; Process; Production; Proteins; Protocols documentation; Reporting; Research; Signal Transduction; Small Business Innovation Research Grant; Source; Substrate Interaction; Surface; System; Technology; Testing; Therapeutic; Time; Toxic effect; Universities; Urea; Wisconsin; Xenobiotics; alpha-Fetoproteins; base; cell behavior; cost effective; cytokine; density; drug development; drug use screening; immortalized cell; improved; improved functioning; induced pluripotent stem cell; infrared spectroscopy; large scale production; monolayer; novel; novel strategies; phase 1 study; physical property; public health relevance; response; screening; stem cell differentiation; stem cells; tool; user-friendly

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.

描述（由申请人提供）：原生素将使用SBIR Shift资金开发一个阵列系统，该阵列系统可以识别化学定义的表面以优化诱导的多能干细胞（HIPSC）分化和成熟。该平台最初将通过其Capacty进行验证，以帮助增加干细胞衍生的肝细胞的功能成熟度，尤其是细胞色素P450（CYP）活性，并随后用于大规模生产HIPSC衍生的肝细胞。尽管人类多能干细胞的承诺得到了广泛认可，可以为许多毁灭性的退行性疾病和新的筛查工具提供新的疗法，以更快，具有成本效益的药物开发，但没有报道说，这些应用具有足够的功能成熟度的细胞。 Primorigen的技术将通过开发一个新型的肽阵列来解决这种需求，以评估不溶性细胞信号对干细胞衍生谱系成熟的影响。第一阶段的研究将验证阵列稳定性和能力确定条件 这可以改善原发性和HIPSC衍生的肝细胞的功能和CYP活性。第二阶段将把这种方法应用于其他谱系，包括HPSC衍生的心肌细胞，并适应最佳条件以高容量的肝细胞产生。计划的产品包括：1）用户友好的阵列套件，以识别最佳的表面处理，最终，2）在大量量中产生的功能成熟细胞以支持药物筛查应用。