Document Detail


Engraftment potential of spheroid-forming hepatic endoderm derived from human embryonic stem cells.
MedLine Citation:
PMID:  23373441     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Transplantation and drug discovery programs for liver diseases are hampered by the shortage of donor tissue. While recent studies have shown that hepatic cells can be derived from human embryonic stem cells (hESCs), few cases have shown selective enrichment of hESC-derived hepatocytes and their integration into host liver tissues. Here we demonstrate that the dissociation and reaggregation procedure after an endodermal differentiation of hESC produces spheroids mainly consisted of cells showing hepatic phenotypes in vitro and in vivo. A combined treatment with Wnt3a and bone morphogenic protein 4 efficiently differentiated hESCs into definitive endoderm in an adherent culture. Dissociation followed by reaggregation of these cells in a nonadherent condition lead to the isolation of spheroid-forming cells that preferentially expressed early hepatic markers from the adherent cell population. Further differentiation of these spheroid cells in the presence of the hepatocyte growth factor, oncostatin M, and dexamethasone produced a highly enriched population of cells exhibiting characteristics of early hepatocytes, including glycogen storage, indocyanine green uptake, and synthesis of urea and albumin. Furthermore, we show that grafted spheroid cells express hepatic features and attenuate the serum aspartate aminotransferase level in a model of acute liver injury. These data suggest that hepatic progenitor cells can be enriched by the spheroid formation of differentiating hESCs and that these cells have engraftment potential to replace damaged liver tissues.
Authors:
Sung-Eun Kim; Su Yeon An; Dong-Hun Woo; Jiyou Han; Jong Hyun Kim; Yu Jin Jang; Jeong Sang Son; Hyunwon Yang; Yong Pil Cheon; Jong-Hoon Kim
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-03-12
Journal Detail:
Title:  Stem cells and development     Volume:  22     ISSN:  1557-8534     ISO Abbreviation:  Stem Cells Dev.     Publication Date:  2013 Jun 
Date Detail:
Created Date:  2013-05-30     Completed Date:  2013-12-17     Revised Date:  2014-06-17    
Medline Journal Info:
Nlm Unique ID:  101197107     Medline TA:  Stem Cells Dev     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1818-29     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Albumins / biosynthesis
Animals
Biological Markers
Bone Morphogenetic Protein 4 / pharmacology
Carbon Tetrachloride
Cell Culture Techniques
Cell Differentiation
Dexamethasone / pharmacology
Drug-Induced Liver Injury / metabolism,  pathology,  therapy*
Embryonic Stem Cells / cytology*,  metabolism
Endoderm / cytology,  metabolism,  transplantation*
Glycogen / biosynthesis
Graft Survival
Hepatocyte Growth Factor / pharmacology
Hepatocytes / cytology,  metabolism,  transplantation*
Humans
Mice
Mice, Nude
Oncostatin M / pharmacology
Spheroids, Cellular / cytology,  metabolism,  transplantation*
Transplantation, Heterologous
Urea / metabolism
Wnt3A Protein / pharmacology
Chemical
Reg. No./Substance:
0/Albumins; 0/BMP4 protein, human; 0/Biological Markers; 0/Bone Morphogenetic Protein 4; 0/HGF protein, human; 0/WNT3A protein, human; 0/Wnt3A Protein; 106956-32-5/Oncostatin M; 67256-21-7/Hepatocyte Growth Factor; 7S5I7G3JQL/Dexamethasone; 8W8T17847W/Urea; 9005-79-2/Glycogen; CL2T97X0V0/Carbon Tetrachloride
Comments/Corrections

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