Pharmacogenetic profiling of human embryonic stem cells

Predicting response to drug or xenobiotic exposure is vital to risk assessment and clinical response rates. Primary human hepatocytes are commonly used to evaluate liver drug metabolism and toxicity. They are the most physiologically relevant in vitro model, retaining expression of most ADME-relevant genes. However, human hepatocytes are source limited, have high donor variability, only survive short term in culture, and lack selection for specific genetic profiles. To overcome the limitations associated with primary hepatocytes we and others are investigating the potential of pluripotent stem cells as an alternative or complementary source for generating hepatocytes. Pluripotent stem cells offer advantages over primary hepatocytes because stem cells have high replicative capacity, potentially providing a limitless source of hepatocytes. Stem cell derived hepatocytes (SCDHs) may also provide an improved in vitro system for evaluating pharmacogenetic relationships, e.g. cytochrome P450 (CYP) enzymes and their impact on drug metabolism and toxicity. To demonstrate the utility of SCDHs in pharmacogenetic screening, we genotyped the five commonly used WiCell® human embryonic stem cell lines (hESC), H1, H7, H9, H13 and H14. Testing the utility of stem cell derived hepatocytes for pharmacogenic screening