Journal
BIOMATERIALS
Volume 34, Issue 7, Pages 1781-1789Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2012.11.029
Keywords
Hepatocyte-like cell; Human ES cell; Human iPS cell; Nanopillar plate; Drug screening
Funding
- Ministry of Health, Labor, and Welfare of Japan
- Japan Research foundation For Clinical Pharmacology
- Uehara Memorial Foundation
- Japan Society for the Promotion of Science
- National Institute of Biomedical Innovation (NIBIO)
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Although it is expected that hepatocyte-like cells differentiated from human embryonic stem (ES) cells or induced pluripotent stem (iPS) cells will be utilized in drug toxicity testing, the actual applicability of hepatocyte-like cells in this context has not been well examined so far. To generate mature hepatocyte-like cells that would be applicable for drug toxicity testing, we established a hepatocyte differentiation method that employs not only stage-specific transient overexpression of hepatocyte-related transcription factors but also a three-dimensional spheroid culture system using a Nanopillar Plate. We succeeded in establishing protocol that could generate more matured hepatocyte-like cells than our previous protocol. In addition, our hepatocyte-like cells could sensitively predict drug-induced hepatotoxicity, including reactive metabolite-mediated toxicity. In conclusion, our hepatocyte-like cells differentiated from human ES cells or iPS cells have potential to be applied in drug toxicity testing. (C) 2012 Elsevier Ltd. All rights reserved.
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