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Accurate prediction of Drug Induced Liver Injury using stem cell-derived populations.

TitleAccurate prediction of Drug Induced Liver Injury using stem cell-derived populations.
Publication TypeJournal Article
Year of Publication2014
AuthorsSzkolnicka D, Farnworth SL, Lucendo-Villarin B, Storck C, Zhou W, Iredale JP, Flint O, Hay DC
JournalStem Cells Transl Med
Date Published2014 Feb
KeywordsCell Differentiation, Cell Survival, Cells, Cultured, Culture Media, Serum-Free, Cytotoxins, Dose-Response Relationship, Drug, Drug-Induced Liver Injury, Embryonic Stem Cells, Hepatocytes, Humans, Pluripotent Stem Cells, Predictive Value of Tests, Stem Cell Transplantation

Despite major progress in the knowledge and management of human liver injury, there are millions of people suffering from chronic liver disease. Currently, the only cure for end-stage liver disease is orthotopic liver transplantation; however, this approach is severely limited by organ donation. Alternative approaches to restoring liver function have therefore been pursued, including the use of somatic and stem cell populations. Although such approaches are essential in developing scalable treatments, there is also an imperative to develop predictive human systems that more effectively study and/or prevent the onset of liver disease and decompensated organ function. We used a renewable human stem cell resource, from defined genetic backgrounds, and drove them through developmental intermediates to yield highly active, drug-inducible, and predictive human hepatocyte populations. Most importantly, stem cell-derived hepatocytes displayed equivalence to primary adult hepatocytes, following incubation with known hepatotoxins. In summary, we have developed a serum-free, scalable, and shippable cell-based model that faithfully predicts the potential for human liver injury. Such a resource has direct application in human modeling and, in the future, could play an important role in developing renewable cell-based therapies.

Alternate JournalStem Cells Transl Med
PubMed ID24375539
PubMed Central IDPMC3925059
Grant List / / Biotechnology and Biological Sciences Research Council / United Kingdom
/ / Medical Research Council / United Kingdom
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