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Pluripotent stem cell derived hepatocyte like cells and their potential in toxicity screening.

TitlePluripotent stem cell derived hepatocyte like cells and their potential in toxicity screening.
Publication TypeJournal Article
Year of Publication2010
AuthorsGreenhough S, Medine C.N, Hay DC
JournalToxicology
Volume278
Issue3
Pagination250-5
Date Published2010 Dec 30
ISSN1879-3185
KeywordsCell Differentiation, Cytotoxins, Hepatocytes, Humans, Liver, Models, Biological, Pluripotent Stem Cells, Toxicity Tests
Abstract

Despite considerable progress in modelling human liver toxicity, the requirement still exists for efficient, predictive and cost effective in vitro models to reduce attrition during drug development. Thousands of compounds fail in this process, with hepatotoxicity being one of the significant causes of failure. The cost of clinical studies is substantial, therefore it is essential that toxicological screening is performed early on in the drug development process. Human hepatocytes represent the gold standard model for evaluating drug toxicity, but are a limited resource. Current alternative models are based on immortalised cell lines and animal tissue, but these are limited by poor function, exhibit species variability and show instability in culture. Pluripotent stem cells are an attractive alternative as they are capable of self-renewal and differentiation to all three germ layers, and thereby represent a potentially inexhaustible source of somatic cells. The differentiation of human embryonic stem cells and induced pluripotent stem cells to functional hepatocyte like cells has recently been reported. Further development of this technology could lead to the scalable production of hepatocyte like cells for liver toxicity screening and clinical therapies. Additionally, induced pluripotent stem cell derived hepatocyte like cells may permit in vitro modelling of gene polymorphisms and genetic diseases.

DOI10.1016/j.tox.2010.07.012
Alternate JournalToxicology
PubMed ID20674645