A. De La Forest, M. Andersen, D. Galitz, and J. Aho
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. Hepatocyte-like cells, derived from human pluripotent stem cells, are emerging as a stable and renewable model for drug-induced liver toxicity testing. Developing standardized differentiation protocols that reliably generate functional hepatocytes is important for the future use of stem cell-derived hepatocytes for toxicology and drug discovery. In this study, we demonstrate the reliability and efficiency our StemXVivo® Hepatocyte Differentiation Kit, which uses a standardized protocol with high quality reagents to generate functional hepatocyte-like cells from human pluripotent stem cells. The StemXVivo® Hepatocyte Differentiation Kit yielded a highly enriched population of pluripotent stem cell-derived hepatocyte-like cells that were functionally characterized by staining for lipid and glycogen storage, quantitative analysis of albumin and urea secretion, and assessment of p450 activity. Kit-derived hepa tocyte-like cells were evaluated for use as a high throughput in vitro model for liver toxicity by assessing their response to known hepatotoxic molecules using a high-content imaging assay. These results demonstrate 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.
