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: 8739664
• 负责人: Jae-Sung Lee
• 金额: $ 20万
• 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 2016-08-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8739664
• 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; Stem cells; 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; 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）：Primorigen将使用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。该平台最初将验证其帮助提高干细胞源性肝细胞功能成熟度的能力，特别是细胞色素p450 （CYP）活性，随后将用于大规模生产hipsc源性肝细胞。尽管人们普遍认为人类多能干细胞有望为许多破坏性退行性疾病提供新的治疗方法，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。第一阶段的研究将验证阵列的稳定性和识别条件的能力