Stem-cell derived hepatocyte-like cells for the assessment of drug-induced liver injury

Abstract

Drug-induced liver injury is a major cause of drug discovery failure in clinical trials and a leading cause of liver disease. Current preclinical drug testing does not predict hepatotoxicity which highlights the importance of developing highly predictive cell-based models. The use of stem cell technology and differentiation into hepatocyte-like cells (HLCs) could provide a stable source of hepatocytes for multiple applications, including drug screening. HLCs derived from both embryonic and induced pluripotent stem cells have been used to accurately predict hepatotoxicity as well as to test individual-specific toxicity. Although there are still many limitations, mainly related to the lack of fully maturity of the HLCs derived from pluripotent stem cells, they could provide a relative unlimited and consistent supply of cells with stable phenotype, that could be obtained from different donors, enabling the generation of a library of HLCs representative of the variability of human population.

Keywords: Embryonic stem cells; Hepatocyte-like cells; Hepatotoxicity; Induced-pluripotent stem cells.