title: Generation of hybrid hepatocytes by cell fusion from monkey embryoid body cells in the injured mouse liver.
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 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.
authors.affiliation: Department of Pathological Biochemistry, Medical Research Institute, Tokyo Medical and Dental University, 2-3-10 Kandasurugadai, Chiyoda-ku, Tokyo, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Okamura
authors.forename: Kinji
authors.initials: K
authors.lastname: Asahina
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Fujimori
authors.forename: Rie
authors.initials: R
authors.lastname: Ozeki
authors.forename: Keiko
authors.initials: K
authors.lastname: Shimizu-Saito
authors.forename: Yujiro
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Kenichi
authors.initials: K
authors.lastname: Teramoto
authors.forename: Shigeki
authors.initials: S
authors.lastname: Arii
authors.forename: Kozo
authors.initials: K
authors.lastname: Takase
authors.forename: Miho
authors.initials: M
authors.lastname: Kataoka
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Soeno
authors.forename: Chise
authors.initials: C
authors.lastname: Tateno
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Yoshizato
authors.forename: Hirobumi
authors.initials: H
authors.lastname: Teraoka
mesh_terms: 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
chemical_list: D017931:DNA Primers; D014568:Urokinase-Type Plasminogen Activator