Utility of embryonic stem (ES) cells as a source of human hepatocytes. There have been recent advances in the ability to differentiate ES cells into a variety of specific cell fates including oligodendrocytes, cardiomyocytes and hepatocytes. We are working on developing optimal conditions for hepatocyte differentiation using both NIH-approved ES cell lines, as well as induced pluripotent stem cell lines (iPSCs). Human hepatocytes are a key component of preclinical drug development because animal models are not always capable of fully replicating what occurs in people. In addition, idiosyncratic hepatotoxicity is one of the main reasons for FDA withdrawal of drug approval. Because human hepatocytes are a finite resource, with no consistent quality control or genetic profile, the ability to differentiate hepatocytes from stem cells is highly desirable. Given that CYP450 function is a hallmark of liver function, we are defining our approaches based on the ability to express metabolically active enzymes.