Generation of hybrid hepatocytes by cell fusion from monkey embryoid body cells in the injured mouse liver

Histochemistry and Cell Biology Volume 125 Issue 3 Page 247-257 published_at 2006-03
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Title ( eng )
Generation of hybrid hepatocytes by cell fusion from monkey embryoid body cells in the injured mouse liver
Okamura Kentaro
Asahina Kinji
Fujimori Hiroaki
Ozaki Rie
Shimizu-Saito Keiko
Tanaka Yujiro
Teramoto Kenichi
Arii Shigeki
Takase Kozo
Kataoka Miho
Soeno Yoshinori
Tateno Chie
Teraoka Hirofumi
Source Title
Histochemistry and Cell Biology
Volume 125
Issue 3
Start Page 247
End Page 257
Monkey embryonic stem (ES) cells have characteristics that are similar to human ES cells, and might be useful as a substitute model for preclinical research. When embryoid bodies (EBs) formed from monkey ES cells were cultured, expression of many hepatocyte-related genes including cytochrome P450 (Cyp) 3a and Cyp7a1 was observed. Hepatocytes were immunocytochemically observed using antibodies against albumin (ALB), cytokeratin-8/18, and α1-antitrypsin in the developing EBs. The in vitro differentiation potential of monkey ES cells into the hepatic lineage prompted us to examine the transplantabilityof monkey EB cells. As an initial approach to assess the repopulation potential, we transplanted EB cells into immunodeficient urokinase-type plasminogen activator transgenic mice that undergo liver failure. After transplantation, the hepatocyte colonies expressing monkey ALB were observed in the mouse liver. Fluorescence in-situ hybridization revealed that the repopulating hepatocytes arise from cell fusion between transplanted monkey EB cells and recipient mouse hepatocytes. In contrast, neither cell fusion nor repopulation of hepatocytes was observed in the recipient liver after undifferentiated ES cell transplantation. These results indicate that the differentiated cells in developing monkey EBs, but not contaminating ES cells, generate functional hepatocytes by cell fusion with recipient mouse hepatocytes, and repopulate injured mouse liver.
embryonic stem cells
hepatocyte differentiation
transgenic mouse
xenogeneic transplantation
Biology [ 460 ]
Medical sciences [ 490 ]
Resource Type journal article
Date of Issued 2006-03
Copyright (c) 2005 Springer-Verlag
Publish Type Author’s Original
Access Rights open access
Source Identifier
The original version is abailable at
[NCID] AA11033302
[ISSN] 0948-6143
[DOI] 10.1007/s00418-005-0065-1
[PMID] 16195892
[DOI] isVersionOf