| Rapid generation of mature hepatocyte-like cells from human induced pluripotent stem cells by an efficient three-step protocol. | |
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MedLine Citation:
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PMID: 22095466 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Liver transplantation is the only definitive treatment for end-stage cirrhosis and fulminant liver failure but the lack of available donor livers is a major obstacle to liver transplantation. Recently, induced pluripotent stem (iPS) cells, derived from the reprogramming of somatic fibroblasts, have been shown to resemble embryonic stem (ES) cells in that they have pluripotent properties and the potential to differentiate into all cell lineages in vitro, including hepatocytes. Thus iPS cells could serve as a favorable cell source for a wide range of applications, including drug toxicity testing, cell transplantation, and patient-specific disease modeling. Here we describe an efficient and rapid three-step protocol that is able to rapidly generate hepatocyte-like cells from human iPS cells. This occurs because the endodermal induction step allows for more efficient and definitive endoderm cell formation. We show that hepatocyte growth factor (HGF), which synergizes with Activin A and Wnt3a, elevates the expression of the endodermal marker Foxa2 (Forkhead box a2) by 39.3% compared to when HGF is absent (14.2%) during the endodermal induction step. In addition, iPSC-derived hepatocytes had a similar gene expression profile to mature hepatocytes. Importantly, the hepatocyte-like cells exhibited cytochrome P450 3A4 (CYP3A4) enzyme activity, secreted urea, uptake of low-density lipoprotein (LDL), and possessed the ability to store glycogen. Moreover, the hepatocyte-like cells rescued lethal fulminant hepatic failure in a nonobese diabetic severe combined immunodeficienct mouse model. CONCLUSION: We have established a rapid and efficient differentiation protocol that is able to generate functional hepatocyte-like cells from human iPS cells. This may offer an alternative option for treatment of liver diseases. (HEPATOLOGY 2011.). |
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Authors:
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Yu-Fan Chen; Chien-Yu Tseng; Hsei-Wei Wang; Hung-Chih Kuo; Vincent W Yang; Oscar K Lee |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-11-16 |
Journal Detail:
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Title: Hepatology (Baltimore, Md.) Volume: - ISSN: 1527-3350 ISO Abbreviation: - Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-11-18 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8302946 Medline TA: Hepatology Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011 American Association for the Study of Liver Diseases. |
Affiliation:
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Department of Medical Research and Education, Taipei Veterans General Hospital, Taiwan; Stem Cell Research Center, National Yang-Ming University, Taiwan. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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