Stem cell-derived hepatocytes as a predictive model for drug-induced liver injury: are we there yet?
Amongst the different types of adverse drug reactions, drug-induced liver injury is the most prominent cause of patient morbidity and mortality. However, the current available hepatic model systems developed for evaluating safety have limited utility and relevance as they do not fully recapitulate a fully functional hepatocyte, and do not sufficiently represent the genetic polymorphisms present in the population. The rapidly advancing research in stem cells raises the possibility of using human pluripotent stem cells in bridging this gap. The generation of human induced pluripotent stem cells via reprogramming of mature human somatic cells may also allow for disease modelling in vitro for the purposes of assessing drug safety and toxicology. This would also allow for better understanding of disease processes and thus facilitate in the potential identification of novel therapeutic targets. This review will focus on the current state of effort to derive hepatocytes from human pluripotent stem cells for potential use in hepatotoxicity evaluation and aims to provide an insight as to where the future of the field may lie.
Department of Molecular and Clinical Pharmacology, University of Liverpool, MRC Centre for Drug Safety Science, Liverpool, UK.
Richard
R
Kia
Rowena L C
RL
Sison
James
J
Heslop
Neil R
NR
Kitteringham
Neil
N
Hanley
John S
JS
Mills
B Kevin
BK
Park
Chris E P
CE
Goldring
D002454:Cell Differentiation; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D053595:Embryonic Stem Cells / Q000166:cytology; D022781:Hepatocytes / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D039904:Pluripotent Stem Cells / Q000166:cytology*