Development of an iPSC-derived human hepatocyte platform for drug development.

DESCRIPTION (provided by applicant): Human inducible pluripotent stem cells (iPSCs) proliferate readily and can be terminally differentiated into hepatocytes, which potentially makes them an attractive, cost-effective resource compared to primary human hepatocytes. Moreover, the ability to standardize a platform to a single human donor, or donor(s) who may include known genetic drug metabolism polymorphism(s), can eliminate or greatly reduce donor-donor variability associated with primary hepatocytes. Unfortunately, it has been clearly demonstrated that differentiated iPSC-derived hepatocytes (iHCs), though similar to primary hepatocytes in many ways, retain certain fetal -like aspects. This includes increased expression of fetal-like proteins, e.g.??fetalprotein, and decreased activity of specific cytochrome p450 enzymes, e.g. the CYP3A family, which is responsible for metabolizing over 60% of drugs. Thus, the pharmaceutical industry and regulatory agencies view the use of iHCs as promising but curren