Generation of hybrid hepatocytes by cell fusion from monkey embryoid body cells in the injured mouse liver.
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 alpha1-antitrypsin in the developing EBs. The in vitro differentiation potential of monkey ES cells into the hepatic lineage prompted us to examine the transplantability of 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.
Okamura
Kentaro
K
Department of Pathological Biochemistry, Medical Research Institute, Tokyo Medical and Dental University, 2-3-10 Kandasurugadai, Chiyoda-ku, Tokyo, Japan.
Asahina
Kinji
K
Fujimori
Hiroaki
H
Ozeki
Rie
R
Shimizu-Saito
Keiko
K
Tanaka
Yujiro
Y
Teramoto
Kenichi
K
Arii
Shigeki
S
Takase
Kozo
K
Kataoka
Miho
M
Soeno
Yoshinori
Y
Tateno
Chise
C
Yoshizato
Katsutoshi
K
Teraoka
Hirobumi
H
D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D002459:Cell Fusion; D017931:DNA Primers / Q000235:genetics; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology* / Q000378:metabolism; D006822:Hybrid Cells / Q000166:cytology* / Q000378:metabolism; D007150:Immunohistochemistry; D008099:Liver / Q000166:cytology / Q000293:injuries* / Q000378:metabolism; D008252:Macaca fascicularis; D051379:Mice; D016513:Mice, SCID; D008822:Mice, Transgenic; D033581:Stem Cell Transplantation; D014183:Transplantation, Heterologous; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics / Q000378:metabolism
D017931:DNA Primers; D014568:Urokinase-Type Plasminogen Activator