Document Detail

Rapid generation of mature hepatocyte-like cells from human induced pluripotent stem cells by an efficient three-step protocol.
MedLine Citation:
PMID:  22095466     Owner:  NLM     Status:  MEDLINE    
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 cells (iPSCs) 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, iPSCs 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 iPSCs. 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 immunodeficient mouse model. Conclusion: We have established a rapid and efficient differentiation protocol that is able to generate functional hepatocyte-like cells from human iPSCs. This may offer an alternative option for treatment of liver diseases.
Yu-Fan Chen; Chien-Yu Tseng; Hsei-Wei Wang; Hung-Chih Kuo; Vincent W Yang; Oscar K Lee
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-03-01
Journal Detail:
Title:  Hepatology (Baltimore, Md.)     Volume:  55     ISSN:  1527-3350     ISO Abbreviation:  Hepatology     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-03-30     Completed Date:  2012-05-22     Revised Date:  2013-10-16    
Medline Journal Info:
Nlm Unique ID:  8302946     Medline TA:  Hepatology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1193-203     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 American Association for the Study of Liver Diseases.
Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan.
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MeSH Terms
Carbon Tetrachloride / adverse effects
Cell Differentiation / drug effects,  physiology*
Cell Lineage*
Cell Transplantation / methods*
Cells, Cultured
Disease Models, Animal
Gene Expression Profiling
Glutamine / pharmacology
Hepatocyte Growth Factor / pharmacology
Hepatocytes / cytology*,  physiology,  transplantation
Liver Failure / chemically induced,  therapy
Mice, SCID
Oncostatin M / pharmacology
Pluripotent Stem Cells / cytology*,  physiology
Treatment Outcome
Grant Support
Reg. No./Substance:
106956-32-5/Oncostatin M; 56-23-5/Carbon Tetrachloride; 56-85-9/Glutamine; 67256-21-7/Hepatocyte Growth Factor

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