title: Stem Cell Strategies to Evaluate Idiosyncratic Drug-induced Liver Injury.
abstract: The host-dependent nature of idiosyncratic drug-induced liver injury (iDILI) suggests that rare genetic polymorphisms may contribute to the disease. Indeed, a few mutations in key genes have already been identified using conventional human genetics approaches. Over 50 commonly used drugs can precipitate iDILI, making this a substantial medical problem. Only recently have human induced pluripotent stem cells been used as a research tool to discover novel iDILI genes and to study the mechanisms of iDILI in vitro. Here we review the current state of stem cell use in the investigation of iDILI, with a special focus on genetics. In addition, the concerns and difficulties associated with genetics and animal model research are discussed. We then present the features of patient-specific pluripotent stem cells (which may be derived from iDILI patients themselves), and explain why these cells may be of great utility. A variety of recent approaches to produce hepatocyte-like cells from pluripotent cells and the associated advantages and limitations of such cells are discussed. Future directions for the use of stem cell science to investigate iDILI include novel ways to identify new iDILI genes, a consideration of epigenetic impacts on iDILI, and the development of new and improved strategies for the production of hepatocytes from human pluripotent cells.
authors.affiliation: Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT, USA.
authors.forename: Winfried
authors.initials: W
authors.lastname: Krueger
authors.affiliation: Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT, USA.
authors.forename: Urs A
authors.initials: UA
authors.lastname: Boelsterli
authors.affiliation: Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT, USA ; Department of Molecular and Cell Biology, University of Connecticut, Storrs, CT, USA ; University of Connecticut Stem Cell Institute, Storrs/Farmington, CT, USA.
authors.forename: Theodore P
authors.initials: TP
authors.lastname: Rasmussen
keywords: DILI; Embryonic stem cell; Genetics; Toxicity; iPS