Histochemistry and Cell Biology

, Volume 125, Issue 3, pp 247–257 | Cite as

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

  • Kentaro Okamura
  • Kinji Asahina
  • Hiroaki Fujimori
  • Rie Ozeki
  • Keiko Shimizu-Saito
  • Yujiro Tanaka
  • Kenichi Teramoto
  • Shigeki Arii
  • Kozo Takase
  • Miho Kataoka
  • Yoshinori Soeno
  • Chise Tateno
  • Katsutoshi Yoshizato
  • Hirobumi Teraoka
Original paper

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

Cynomolgus Embryonic stem cells Hepatocyte differentiation Transgenic mouse Xenogeneic transplantation 

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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Kentaro Okamura
    • 1
  • Kinji Asahina
    • 1
  • Hiroaki Fujimori
    • 1
  • Rie Ozeki
    • 1
  • Keiko Shimizu-Saito
    • 1
  • Yujiro Tanaka
    • 2
  • Kenichi Teramoto
    • 2
  • Shigeki Arii
    • 2
  • Kozo Takase
    • 2
  • Miho Kataoka
    • 3
  • Yoshinori Soeno
    • 3
    • 4
  • Chise Tateno
    • 3
  • Katsutoshi Yoshizato
    • 3
    • 5
  • Hirobumi Teraoka
    • 1
  1. 1.Department of Pathological Biochemistry, Medical Research InstituteTokyo Medical and Dental UniversityChiyoda-ku, TokyoJapan
  2. 2.Graduate School of Medicine and DentistryTokyo Medical and Dental UniversityTokyoJapan
  3. 3.Yoshizato Project, CLUSTERPrefectural Institute of Industrial Science and TechnologyHiroshimaJapan
  4. 4.PhoenixBio Co, LtdHiroshimaJapan
  5. 5.Developmental Biology Laboratory, Department of Biological Science, Graduate School of ScienceHiroshima UniversityHiroshimaJapan

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