Histochemistry and Cell Biology

, Volume 125, Issue 3, pp 247–257

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

Authors

  • Kentaro Okamura
    • Department of Pathological Biochemistry, Medical Research InstituteTokyo Medical and Dental University
    • Department of Pathological Biochemistry, Medical Research InstituteTokyo Medical and Dental University
  • Hiroaki Fujimori
    • Department of Pathological Biochemistry, Medical Research InstituteTokyo Medical and Dental University
  • Rie Ozeki
    • Department of Pathological Biochemistry, Medical Research InstituteTokyo Medical and Dental University
  • Keiko Shimizu-Saito
    • Department of Pathological Biochemistry, Medical Research InstituteTokyo Medical and Dental University
  • Yujiro Tanaka
    • Graduate School of Medicine and DentistryTokyo Medical and Dental University
  • Kenichi Teramoto
    • Graduate School of Medicine and DentistryTokyo Medical and Dental University
  • Shigeki Arii
    • Graduate School of Medicine and DentistryTokyo Medical and Dental University
  • Kozo Takase
    • Graduate School of Medicine and DentistryTokyo Medical and Dental University
  • Miho Kataoka
    • Yoshizato Project, CLUSTERPrefectural Institute of Industrial Science and Technology
  • Yoshinori Soeno
    • Yoshizato Project, CLUSTERPrefectural Institute of Industrial Science and Technology
    • PhoenixBio Co, Ltd
  • Chise Tateno
    • Yoshizato Project, CLUSTERPrefectural Institute of Industrial Science and Technology
  • Katsutoshi Yoshizato
    • Yoshizato Project, CLUSTERPrefectural Institute of Industrial Science and Technology
    • Developmental Biology Laboratory, Department of Biological Science, Graduate School of ScienceHiroshima University
  • Hirobumi Teraoka
    • Department of Pathological Biochemistry, Medical Research InstituteTokyo Medical and Dental University
Original paper

DOI: 10.1007/s00418-005-0065-1

Cite this article as:
Okamura, K., Asahina, K., Fujimori, H. et al. Histochem Cell Biol (2006) 125: 247. doi:10.1007/s00418-005-0065-1

Abstract

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 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.

Keywords

CynomolgusEmbryonic stem cellsHepatocyte differentiationTransgenic mouseXenogeneic transplantation

Copyright information

© Springer-Verlag 2005