Hepatocytes derived from human induced pluripotent stem cells: Towards establishing an in vitro model for assessing population variability in hepatotoxicity testing

Interindividual differences in response to chemicals have been typically addressed through the use of a 10-fold default "uncertainty" factor. It was only recently that <i>in vitro</i> models emerged to quantitatively assess interindividual variability in the human population for specific chemicals. In the current study, we attempted to establish an <i>in vitro</i> model for assessing population variability in hepatotoxicity testing using a panel of hepatocytes derived from nine human induced pluripotent stem cell (iPSC) lines belonging to three different ethnic groups, Black or African American, Latino or Hispanic, and Non-Hispanic White. We demonstrated that the panel of iPSC-derived hepatocytes manifested diversity in hepatic function assays, in global and hepatic gene expressions, and in cytotoxic responses to four well know hepatotoxicants with distinct mechanisms of toxicity: acetaminophen, troglitazone, diglycolic acid, and usnic acid. However, due to the unavailability of model compounds with ethnicity specific toxicity as well as the small number of individuals in each ethnic group (<i>n</i> = 3), ethnic-specific effects were not observed using the model.