Document Detail

Flow cytometric isolation and clonal identification of self-renewing bipotent hepatic progenitor cells in adult mouse liver.
MedLine Citation:
PMID:  18837044     Owner:  NLM     Status:  MEDLINE    
The adult liver progenitor cells appear in response to several types of pathological liver injury, especially when hepatocyte replication is blocked. These cells are histologically identified as cells that express cholangiocyte markers and proliferate in the portal area of the hepatic lobule. Although these cells play an important role in liver regeneration, the precise characterization that determines these cells as self-renewing bipotent primitive hepatic cells remains to be shown. Here we attempted to isolate cells that express a cholangiocyte marker from the adult mouse liver and perform single cell-based analysis to examine precisely bilineage differentiation potential and self-renewing capability of these cells. Based on the results of microarray analysis and immunohistochemistry, we used an antibody against CD133 and isolate CD133(+) cells via flow cytometry. We then cultured and propagated isolated cells in a single cell culture condition and examined their potential for proliferation and differentiation in vitro and in vivo. Isolated cells that could form large colonies (LCs) in culture gave rise to both hepatocytes and cholangiocytes as descendants, while maintaining undifferentiated cells by self-renewing cell divisions. The clonogenic progeny of an LC-forming cell is capable of reconstituting hepatic tissues in vivo by differentiating into fully functional hepatocytes. Moreover, the deletion of p53 in isolated LC-forming cells resulted in the formation of tumors with some characteristics of hepatocellular carcinoma and cholangiocarcinoma upon subcutaneous injection into immunodeficient mutant mice. These data provide evidence for the stem cell-like capacity of isolated and clonally cultured CD133(+) LC-forming cells. Conclusion: Our method for prospectively isolating hepatic progenitor cells from the adult mouse liver will facilitate study of their roles in liver regeneration and carcinogenesis.
Atsushi Suzuki; Sayaka Sekiya; Makiko Onishi; Naoko Oshima; Hiroshi Kiyonari; Hiromitsu Nakauchi; Hideki Taniguchi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Hepatology (Baltimore, Md.)     Volume:  48     ISSN:  1527-3350     ISO Abbreviation:  Hepatology     Publication Date:  2008 Dec 
Date Detail:
Created Date:  2008-12-01     Completed Date:  2009-01-12     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8302946     Medline TA:  Hepatology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1964-78     Citation Subset:  IM    
Division of Organogenesis and Regeneration, Post-Genome Science Center, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
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MeSH Terms
Antigens, CD / metabolism
Carcinoma, Hepatocellular / metabolism,  pathology
Cell Differentiation / physiology
Cell Proliferation
Cells, Cultured
Cloning, Organism
Flow Cytometry
Glycoproteins / metabolism
Hepatocytes / cytology*,  metabolism
Liver / cytology*,  metabolism
Liver Neoplasms / metabolism,  pathology
Liver Regeneration / physiology*
Mice, Knockout
Peptides / metabolism
Stem Cells / cytology*,  metabolism,  physiology
Tumor Suppressor Protein p53 / genetics,  metabolism
Reg. No./Substance:
0/AC133 antigen; 0/Antigens, CD; 0/Glycoproteins; 0/Peptides; 0/Tumor Suppressor Protein p53

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