J. Aho, D. Galitz, J. Sabat, and F. Rinaldi
ABSTRACT
Secondary liver toxicity is a leading cause of commercial pharmaceutical drug recalls and compound failures during drug development. Primary hepatocytes, the most common in vitro model for drug-induced liver toxicity testing, are not ideal for high throughput screening due to their limited availability, difficulty to culture, and functional instability in vitro. Hepatocytelike cells, derived from human pluripotent stem cells, are emerging as a stable and renewable model for drug-induced liver toxicity testing. In this study, we hypothesize that hepatocyte-like cells derived from induced pluripotent stem cells using the StemXVivo® Hepatocyte Differentiation Kit can be used for high throughput toxicity screens. We have previously demonstrated that the StemXVivo® Hepatocyte Differentiation Kit efficiently and consistently generates functional hepatocyte-like cells. To provide further functional validity of these cells we first show that Cyp3A4, an essential hepatic enzyme often analyzed in drug toxicity studies, can be induced in kit-derived hepatocytes. We then used high content imaging to quantitate cell viability against a panel of known hepatotoxic molecules. Our data indicate that the StemXVivo® Hepatocyte Differentiation Kit provides a reliable and renewable source of hepatocyte-like cells that can be utilized for high throughput toxicology and drug discovery.
