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Transplantation of hepatocyte-like cells differentiated from ES cells

Research Project

Project/Area Number 13470232
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

TERAMOTO Kenichi  Tokyo Medical and Dental Uni., surgery, Associate Professor, 大学院・医歯学総合研究科, 助教授 (80197813)

Co-Investigator(Kenkyū-buntansha) TAKASE Kzo  Tokyo Medical and Dental Uni., Professor, 大学院・医歯学総合研究科, 教授 (90211333)
TERAOKA Hirofumi  Tokyo Medical and Dental Uni., M.R.I., Professor, 難治疾患研究所, 教授 (30019137)
ARII Shigeki  Tokyo Medical and Dental Uni., surgery, Professor, 大学院・医歯学総合研究科, 教授 (50151171)
SAITO Keiko  Tokyo Medical and Dental Uni., Lecturer, 難治疾患研究所, 教務職員 (50178969)
TANAK Yujiro  Tokyo Medical and Dental Uni., Professor, 医学部附属病院, 教授 (70236644)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥13,900,000 (Direct Cost: ¥13,900,000)
Fiscal Year 2003: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2002: ¥5,600,000 (Direct Cost: ¥5,600,000)
Fiscal Year 2001: ¥5,200,000 (Direct Cost: ¥5,200,000)
Keywordsmouse embryonic stern cell / hepatocyte differentiation / umbilical cord blood / cell transplantation / liver failure / cell differentiation / 再生医学 / ES細胞 / ヒト臍帯血由来細胞 / stem cell / teratoma / 幹細胞 / 肝再生
Research Abstract

1)A study of induction of hepatocytefrom ES cell
We have succeeded in inducing albumin-producing cell through EB from ES cell. These cell had a ability of producing urea. Taken these together, these cells are considered to be hepatocyte. This hepatocyte-like cell was transplanted into C57BL/6 mouse which had liver injury in advance. The transplanted cell grew up in the recipient liver and produced albumin. But, teratoma formation was seen in 20-30% mouse. The cell was selected in order to suppress teratoma. First, the single layer cell culture from EB was performed, and isolated. The cell was selected by specific gravity by the ercoll method. This cell group was negative in oct 3/4. When this cell was transplanted to an above-mentioned liver injury model mouse, teratoma formation was not recognized. As mentioned above, recovery of the cell group which does not generate teratoma from an embryonic stem cell was attained. Furthermore, it became possible by removing other blood cell ingredients for this cell group using FAGS and MACS to obtain many albumin positive cells.
2) ES cell of cynomolgus monkey
Aiming at clinical application of embryonic stem cell, induction of a liver cell was tried from cynomolgus monkey embryonic stem cell. Although a different method of induction from a mouse embryonic stem cell was required for induction of cynomolgus monkey stem cell, albumin-producing cell was able to be induced by our method.
3) Induction of hepatocyte from umbilical cord blood
We succeeded in liver cell induction from umbilical cord blood. Two cell types were recognized, one is expressing albumin and CK-18 and the other is expressing albumin and CK-19. Now, we are studying bile duct epithelium cell induction from umbilical cord blood.

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report

Research Products

(15 results)

All Other

All Publications (15 results)

  • [Publications] Chinzei R, Tanaka Y, Shimizu-Saito K, Hara Y, Kakinuma S, Watanabe M, Teramoto K, Arii S, Takase IK, Sato C, Terada N, Teraoka H: "Embryoid-body cells derived from a mouse embryonic stem cell line show differentiation into functional hepatocytes."Hepatology. 36. 22-29 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kakinuma S, Tanaka Y, Chinzei R, Watanabe M, Shimizu-Saito K, Hara Y, Teramoto K, Arii S, Sato C, Takase K, Yasumizu T, Teraoka H: "Human umbilical blood as a source of transplantable hepatic progenitor cells."Stem Cells. 21. 217-227 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Okamura K, Asahina K, Fujimori H, Ozeki R, Shimizu-Saito K, Tanaka Y, Teramoto K, Arii S, Takase K, Teraoka H: "Differentiation of monkey embryonic stem cells into hepatocyte-like cells."Biochem.Biophys.Res.Commun.. (in submission).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Asahina K, KUmashiro Y, Okamura K, Shimizu-Saito K, Tanaka Y, Teramoto K, Arii S, Teraoka H: "Expression of a liver-specific gene, Cyp7a1,reveals hepatic differentiation in embryoid bodies derived from mouse embryonic stem cells."Genes Cells. (in submission).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ozeki R, Kakimura S, Shimizu-Saito K, Tanaka Y, Teramoto K, Arii S, Takase K, Yasumizu T, Asahina K, Teraoka H: "Functional dendritic cells derived from human umblical cord blood in co-culture with a hepatic stellate cell line LI90."(in preparation).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 朝比奈欣治, 齊藤佳子, 寺岡弘文, 柿沼晴, 寺本研一: "臍帯血有核細胞からの肝臓再生医療の可能性、(特集:臍帯血由来細胞と再生医療・細胞治療の展望、寺岡弘文編)"細胞. 36(2). 56-59 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] K, Arii S, Takase K, Sato C, Terada N, Teraoka H: "Embryoid-body cells derived from a mouse embryonic stem cell line show differentiation into functional hepatocytes."Hepatology. 36. 22-29 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kakinuma S, Tanaka Y, Chinzei R, Watanabe M, Shimizu-Saito K, Hara Y, Teramoto K, Arii S, Sato C, Takase K, Yasumizu T, Teraoka H: "Human umbilical cord blood as a source of transplantable hepatic progenitor cells."Stem Cells 21. 21. 217-227 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Okamura K, Asahina K, Fujimori H, Ozeki R, Shimizu-Saito L, Tanaka Y, Teramoto K, Arii S, Takase K, Teraoka H: "Differentiation of monkey embryonic stem cells into hepatocyte-like cells."Biochem.Biophys.Res.Conimun.. (in submission).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Asahina K, Kumashiro Y, Okamura K, Shimizu-Saito K, Tanaka Y, Teramoto K, Arii S, Teraoka H: "Expression of a liver-specific gene, Cyp7a1, reveals hepatic differentiation in embryoid bodies derived from mouse embryonic stem cells."Genes Cells. (in submission).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ozeki R, Kakinuma S, Shimizu-Saito K, Tanaka, Y, Teramoto.K, Arii S, Takase K, Yasumizu T, Asahina K, Teraoka H: "Functional dendritic cells derived from human umbilical cord blood in co-culture with a hepatic stellate cell line L190."(in preparation).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kakinuma S, et al.: "Human umbilical cord blood as a source of transplantable hepatic progenitor cells"Stem Cells. 21. 217-227 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 寺岡 弘文: "臍帯血由来細胞と再生医療の近未来(特集:臍帯血由来細胞と再生医療・細胞治療の展望 寺岡弘文編)"細胞. 36(2). 42-43 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] 朝比奈 欣治 他: "臍帯血有核細胞からの肝臓再生医療の可能性(特集:臍帯血由来細胞と再生医療・細胞治療の展望 寺岡弘文編)"細胞. 36(2). 56-59 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Chinzei R, Tanaka Y, Shimizu, Saito K, Hara Y, Kakinuma S, Watanabe M, Teramoto K, Arii S, Takase K, Sato C, Terada N, Teraoka H: "Embryoid-body cells derived from a mouse embryonic stem cell line show differentiation into functional hepatocytes"Hep atojogy. 36. 22-29 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2001-03-31   Modified: 2016-04-21  

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