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    
Abstract/OtherAbstract:
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.
Authors:
Yu-Fan Chen; Chien-Yu Tseng; Hsei-Wei Wang; Hung-Chih Kuo; Vincent W Yang; Oscar K Lee
Related Documents :
10974076 - Activation of the estrogen-signaling pathway by p21(waf1/cip1) in estrogen receptor-neg...
3088126 - Adherent spleen cell production of e series prostaglandins in rats bearing variants of ...
21569786 - Automated detection of hepatotoxic compounds in human hepatocytes using heparg cells an...
2734976 - Difference in uptake of 3h-estramustine in two human prostatic carcinoma cell lines, ln...
20083906 - Atg7 deficiency increases resistance of mcf-7 human breast cancer cells to photodynamic...
23421206 - Silver nanocrystals mediated combination therapy of radiation with magnetic hyperthermi...
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.
Affiliation:
Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
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
Humans
Liver Failure / chemically induced,  therapy
Mice
Mice, SCID
Oncostatin M / pharmacology
Pluripotent Stem Cells / cytology*,  physiology
Treatment Outcome
Grant Support
ID/Acronym/Agency:
R01 CA084197/CA/NCI NIH HHS; R01 DK052230/DK/NIDDK NIH HHS; R01 DK093680/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
106956-32-5/Oncostatin M; 56-23-5/Carbon Tetrachloride; 56-85-9/Glutamine; 67256-21-7/Hepatocyte Growth Factor
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  A study of UbcH10 expression and its association with recurrence of meningiomas.
Next Document:  Detection of biological uranium reduction using magnetic resonance.