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2007 Fiscal Year Final Research Report Summary

Studies of regenerative medicine on differentiation into hepatic and bile duct cells for preclinical trial to surgery

Research Project

Project/Area Number 18390343
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General surgery
Research InstitutionTokyo Medical and Dental University

Principal Investigator

TERAOKA Hirobumi  Tokyo Medical and Dental University, Medical Research Institute, Professor (30019137)

Co-Investigator(Kenkyū-buntansha) ARII Shigeki  Tokyo Medical and Dental University, Graduate School of Medicine, Professor (50151171)
TANAKA Yujiro  Tokyo Medical and Dental University, Graduate School of Medicine, Professor (70236644)
ISEKI Sachiko  Tokyo Medical and Dental University, Graduate School of dentistry, Assistant Professor (80251544)
YOSHIOKA Kenichi  Tokyo Medical and Dental University, Medical Research Institute, Assistant Professor (70321916)
TAKASE Kozo  Tokyo Medical and Dental University, Graduate School of Medicine, Professor (90211333)
Project Period (FY) 2006 – 2007
KeywordsES cell / Hepatocyte / Regenerative medicine / Cell transplantation / Bile duct / Hepatoblast / ex utero surgery / iPS cell
Research Abstract

Although the intrahepatic bile duct has been suggested to be a source of hepatic progenitor cells in the severely damaged liver, little attention has been paid to the question of whether hepatic progenitor cells exist in the extrahepatic bile duct (EHBD). We examined the phenotypic changes of the mouse EHBD following the bile duct ligation. After bile duct ligation, the number of c-kit-positive epithelilal cells increased in the EHBD. The ligated EHBD expressed mRNA for hepatic progenitor cell markers. Hepatocyte markers were also transiently detected in the EHBD and gall bladder after a bile duct ligation. Hepatic progenitor cells positive for both c-kit and albumin were found in the cultured EHBD population. These results suggest a potential of the EHBD and gall bladder as useful transplantable sources for liver injury.
Avoiding the limitations of the adult liver niche, transplantation of hepatic stem/progenitor cells into fetal liver is desirable to analyze immature cells in a hepati … More c developmental environment. Here, we established a new monitor tool for cell fate of hepatic progenitor cells transplanted into the mouse fetal liver by using ex utero surgery. When embryonic day (ED) 14.5 hepatoblasts were injected into the ED14.5 fetal liver, the transplanted cells expressed albumin abundantly or α-fetoprotein weakly, and contained glycogen in the neonatal liver, indicating that transplanted hepatoblasts can proliferate and differentiate in concord with surrounding recipient parenchymal cells. The transplanted cells became mature in the liver of 6-week-old mice. Furthermore, this method was applicable to transplantation of hepatoblast-like cells derived from mouse ES cells. These data indicate that this unique technique will provide a new in vivo experimental system for studying cell fate of hepatic stem/progenitor cells and liver organogenesis.
We revealed involvement of VEGF in efficient differentiation into hepatocyte-like cells, biological function of the undifferentiated cell marker gene DPPA4, and epigenetic regulation of the mature hepatocyte marker gene MAT1A. Less

  • Research Products

    (17 results)

All 2009 2008 2007 2006 Other

All Journal Article (13 results) (of which Peer Reviewed: 6 results) Presentation (2 results) Book (1 results) Remarks (1 results)

  • [Journal Article] A novel method of mouse ex utero transplantation of hepatic progenitor cells into the fetal liver2009

    • Author(s)
      Shikanai M, et al.
    • Journal Title

      Biochem. Biophys. Res. Commun. 381

      Pages: 276-282

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] A novel method of mouse ex utero transplantation of hepatic progenitor cells into the fetal liver2009

    • Author(s)
      Shikanai M, Asahina K, Iseki S, Teramoto K, Nishida T, Saito T, Shimizu-Saito K, Ota M, Eto K, Teraoka H
    • Journal Title

      Biochemical and Biophysical Research Communications 381

      Pages: 276-282

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] VEGF promotes proliferation and function of hepatocyte-like cells in embryoid bodies formed from mouse embryonic stem cells2008

    • Author(s)
      Fujimori H, et al.
    • Journal Title

      J. Hepatol. 48

      Pages: 962-973

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Involvement of CCAAT/enhancer binding protein-β in epigenetic regulation of mouse methionine adenosyltransferase 1A gene expression2008

    • Author(s)
      Ikeda R, et al.
    • Journal Title

      Intern. J. Biochem. Cell Biol. 40

      Pages: 1956-1969

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] VEGF promotes proliferation and function of hepatocyte-like cells in embryoid bodies formed from mouse embryonic stem cell2008

    • Author(s)
      Fujimori H, Asahina K, ShimizirSaito K, Ikeda R, Tanaka Y, Teramoto K, Morita I, Teraoka H
    • Journal Title

      Journal of Hepatology 48

      Pages: 962-973

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Involvement of CCAAT/enhancer binding protein-p in epigenetic regulation of mouse methionine adenosyltransferase 1A gene expression2008

    • Author(s)
      Ikeda R, Nishida T, Watanabe F, Shimizu-Saito K, Asahina K, Horikawa S, Teraoka H
    • Journal Title

      International Journal of Biochemistry and Cell Biology 40

      Pages: 1956-1969

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Human cord blood cells transplanted into chronic-damaged liver exhibit similar characteristics to functional hepatocytes2007

    • Author(s)
      Kakinuma S, et al.
    • Journal Title

      Transplant. Proc. 39

      Pages: 240-243

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Hepatic progenitor cells in the mouse extrahepatic bile duct after a bile duct ligation2007

    • Author(s)
      Irie T, et al.
    • Journal Title

      Stem Cells Develop. 16

      Pages: 979-987

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Developmental pluripotency-associated 4 localized in active chromatin inhibits mouse embryonic stem cell differentiation into a primitive ectoderm lineage2007

    • Author(s)
      Masaki H, et al.
    • Journal Title

      J. Biol. Chem. 282

      Pages: 33034-33042

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Human cord blood cells transplanted into chronic-damaged liver exhibit similar characteristics to functional hepatocytes.2007

    • Author(s)
      Kakinuma S, Asahina K, Okamura K, Teramoto K, Tateno C, Yoshizato K, Tanaka Y, Yasumizu T, Sakamoto N, Watanabe M, Teraoka H
    • Journal Title

      Transplantation Proceedings 39

      Pages: 240-243

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Hepatic progenitor cells in the mouse extrahepatic bile duct after a bile ductligation2007

    • Author(s)
      Irie T, Asahina K, Shimizu-Saito K, Teramoto K, Arii S, Teraoka H
    • Journal Title

      Stem Cells and Development 16

      Pages: 979-987

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Developmental pluripotency associated 4 (Dppa4) localized in active chromatin inhibits mouse embryonic stem cell differentiation into a primitive ectoderm lineage2007

    • Author(s)
      Masaki H, Nishida T, Kitajima S, Asahina K, Teraoka H
    • Journal Title

      Journal of Biological Chemistry 282

      Pages: 33034-33042

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Transplantation of embryonic stem cell-derived hepatocytes and risk of teratoma formation.2007

    • Author(s)
      Asahina K, Teramoto K, Arii S, Teraoka H
    • Journal Title

      in STEM CELLS AND CANCER (ed. by Parsons DW), Nova Publishers

      Pages: 1-22

    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] VEGF promotes hepatocyte differentiation in embryoid bodies formed from mouse embryonic stem cells2006

    • Author(s)
      Asahina K, Fujimori H, Shimizu-Saito K, Teraoka H
    • Organizer
      2006 FASEB Summer Research Conferences Liver Growth, Development & Disease
    • Place of Presentation
      Snowmass Village, CO, USA
    • Year and Date
      20060722-20060727
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Hepatocyte differentiation and eratoma formation after transplantation of embryoid body cells derived from murine and primate embryonic stem cells into injured mouse liver2006

    • Author(s)
      Teramoto K, Asahina K, Okamura K, Kumashiro Y, Me T, Shimizu-Saito K, Teraoka H, Arii S
    • Organizer
      World Transplant Congress, Hynes Convention Center
    • Place of Presentation
      Boston, MA, USA
    • Year and Date
      20060722-20060727
    • Description
      「研究成果報告書概要(欧文)」より
  • [Book] Stem Cells and Cancer, Chapter 1 : Transplantation of embryonic stem cell derived heoatocytes and risk of teratoma formation2007

    • Author(s)
      Asahina K, et al.
    • Total Pages
      22
    • Publisher
      Nova Publishers, Inc.
    • Description
      「研究成果報告書概要(和文)」より
  • [Remarks] 「研究成果報告書概要(和文)」より

    • URL

      http://www.tmd.ac.jp/mri/pbc/hyoushi.html

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Published: 2010-06-09  

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