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Research on molecular mechanism of hepatic stem cell proliferation and development of mouse models for stem cell transplantation

Research Project

Project/Area Number 20790485
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Gastroenterology
Research InstitutionThe University of Tokyo

Principal Investigator

KAKINUMA Sei  The University of Tokyo, 大学院・医歯学総合研究科, 寄附講座教員 (30372444)

Research Collaborator KAMIYA Akihide  東京大学, 医科学研究所, 助教 (30321904)
SAKAMOTO Naoya  東京医科歯科大学, 大学院・医歯学総合研究科, 寄附講座准教授 (10334418)
Project Period (FY) 2008 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2009: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords再生医学 / 肝細胞 / 幹細胞 / 発生・分化 / 細胞移植 / 細胞外マトリクス / 細胞
Research Abstract

The first objective of this research project is clarification of molecular mechanisms in proliferation of primary mouse hepatic stem/progenitor cells (HSPCs). Primary mouse HSPCs were sorted using surface markers, and were infected with a viral vector expressing a target gene, then were cultured. Our data demonstrated that transcription factor Prox-1 enhances the proliferation of HSPCs, and Sall4 regulates the cell-fate determination of HSPCs. Second objective is development of mouse models for stem cell transplantation. The HSPCs were transplanted into liver-injured recipient mice. Our data showed that the recipient livers were reconstituted by donor HSPCs, and that donor cells were engrafted in long-term.

Report

(3 results)
  • 2009 Annual Research Report   Final Research Report ( PDF )
  • 2008 Annual Research Report
  • Research Products

    (32 results)

All 2010 2009 2008

All Journal Article (16 results) (of which Peer Reviewed: 15 results) Presentation (10 results) Book (6 results)

  • [Journal Article] Lnk/Sh2b3 regulates integrinαIIbβ3 outside-in signaling in platelets leading to stabilization of developing thrombus in vivo.2010

    • Author(s)
      Takizawa H, Nishimura S, Takayama N, Oda A, Nishikii H, Morita Y, Kakinuma S, Yamazaki S, Okamura S, Tamura N, Goto S, Sawaguchi A, Manabe I, Takatsu K, Nakauchi H, Takaki S, Eto K
    • Journal Title

      J Clin Invest 120

      Pages: 179-190

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Comparison of HCV-associated gene expression and cell signaling pathways in cells with or without HCV replicon and in replicon-cured cells.2010

    • Author(s)
      Nishimura-Sakurai Y, Sakamoto N,Mogushi K, Nagaie S, Nakagawa M,Itsui Y, Sekine-Osajima Y,Tasaka-Fujita M, Onuki-Karakama Y,Suda G, Mishima M, Yamamoto M,Ueyama M, Funaoka Y, Watanabe T,Chen CH, Kakinuma S, Tsuchiya K,Tanaka H, Enomoto N, Watanabe M
    • Journal Title

      J Gastroentorol (in press)

    • NAID

      10027216127

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Mutations in the interferon sensitivity determining region and virological response to combination therapy with pegylated-interferon alpha 2b plus ribavirin in patients with chronic hepatitis C-1b infection.2010

    • Author(s)
      Nakagawa M, Sakamoto N, Ueyama M, Mogushi K, Nagaie S, Itsui Y, Azuma S, Kakinuma S, Tanaka H, Enomoto N, Watanabe M
    • Journal Title

      J Gastroentorol (in press)

    • NAID

      10027216778

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Analyses of cell surface molecules on hepatic stem/progenitor cells in mouse fetal liver.2009

    • Author(s)
      Kakinuma S, Ohta H, Kamiya A, Yamazaki Y, Oikawa T, Okada K, Nakauchi H
    • Journal Title

      J Hepatol 51

      Pages: 127-38

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Hepatic stem/progenitor cells and stem cell transplantation for the treatment of liver disease.2009

    • Author(s)
      Kakinuma S, Nakauchi H, Watanabe M
    • Journal Title

      J Gastroenterol 44

      Pages: 167-72

    • NAID

      10025173601

    • Related Report
      2009 Final Research Report
  • [Journal Article] Enrichment and clonal culture of progenitor cells during mouse postnatal liver development in mice.2009

    • Author(s)
      Kamiya A, Kakinuma S, Yamazaki Y, Nakauchi H
    • Journal Title

      Gastroenterology 137

      Pages: 1114-26

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Sall4 regulates cell fate decision of fetal hepatic stem/progenitor cells.2009

    • Author(s)
      Oikawa T, Kamiya A, Kakinuma S, Zeniya M, Nishinakamura R, Tajiri H, *Nakauchi H
    • Journal Title

      Gastroenterology 136

      Pages: 1000-11

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Antiviral effects of the interferon-induced protein GBP-1 and its interaction with the hepatitis C virus NS5B protein.2009

    • Author(s)
      Itsui Y, Sakamoto N, Kakinuma S, Nakagawa M, Sekine-Osajima Y, Tasaka-Fujita M, Nishimura-Sakurai Y, Suda G, Karakama Y, Mishima K, Yamamoto M, Watanabe T, Ueyama M, Funaoka Y, Azuma S, Watanabe M
    • Journal Title

      Hepatology 50

      Pages: 1727-37

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Sall4 regulates cell fate decision of fetal hepatic stem/progenitor cells2009

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

      Gastroenterorlogy 136

      Pages: 1000-1011

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Enrichment and clonal culture of progenitor cells during mouse postnatal liver development in mice2009

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

      Gastroenterorlogy 137

      Pages: 1114-1126

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Analyses of cell surface molecules on hepatic stem/progenitor cells in mouse fetal liver2009

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

      Journal of Hepatology 51

      Pages: 128-138

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Antiviral effects of the interferon-induced protein GBP-1 and its interaction with the hepatitis C virus NS5B protein2009

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

      Hepatology 50

      Pages: 1727-1737

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sall4 regulates cell fate decision of fetal hepatic stem/progenitor cells2009

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

      Gastroenterology 136

      Pages: 1000-1011

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Analyses of cell surface molecules on hepatic stem/progenitor cells in mouse fetal liver2009

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

      Journal of Hepatology (印刷中)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prospero-related homeobox 1 and liver receptor homolog 1 coordinately regulate long-term proliferation of murine fetal hepatoblasts.2008

    • Author(s)
      Kamiya A, Kakinuma S, Onodera M, Nakauchi H
    • Journal Title

      Hepatology 48

      Pages: 252-264

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Prospero-related homeobox 1 and liver receptor homolog 1 coordinately regulate long-term proliferation of murine fetal hepatoblasts2008

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

      Hepatology 48

      Pages: 252-264

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] マウス胎生中期肝幹/前駆細胞を用いた細胞移植2009

    • Author(s)
      柿沼晴、紙谷聡英、太田春彦、坂本直哉、渡辺守、中内啓光
    • Organizer
      JDDW 2009 (第13回日本肝臓学会大会)
    • Place of Presentation
      京都
    • Year and Date
      2009-10-15
    • Related Report
      2009 Final Research Report
  • [Presentation] マウス肝細胞移植におけるMatrix Metalloproteinaseの関与2009

    • Author(s)
      柿沼晴、紙谷聡英、渡辺守、中内啓光
    • Organizer
      第16回肝細胞研究会(シンポジウム/臨床応用をめざした肝細胞研究の展開)
    • Place of Presentation
      静岡
    • Year and Date
      2009-06-26
    • Related Report
      2009 Final Research Report
  • [Presentation] 肝幹/前駆細胞表面抗原の網羅的解析と細胞移植2009

    • Author(s)
      柿沼晴、紙谷聡英、中内啓光
    • Organizer
      第95回日本消化器病学会総会(ワークショップ/消化器臓器における幹細胞研究の進歩)
    • Place of Presentation
      札幌
    • Year and Date
      2009-05-07
    • Related Report
      2009 Final Research Report
  • [Presentation] 肝幹/前駆細胞表面抗原の網羅的解析と細胞移植2009

    • Author(s)
      柿沼晴, 他
    • Organizer
      第95回日本消化器病学会総会(ワークショップ)
    • Place of Presentation
      札幌
    • Year and Date
      2009-05-07
    • Related Report
      2009 Annual Research Report
  • [Presentation] 肝幹/前駆細胞表面抗原の網羅的解析と細胞移植2008

    • Author(s)
      柿沼晴、紙谷聡英、中内啓光
    • Organizer
      JDDW 2008(第12回日本肝臓学会大会ワークショップ/肝再生;基礎と臨床のBridge研究)
    • Place of Presentation
      東京
    • Year and Date
      2008-10-18
    • Related Report
      2009 Final Research Report
  • [Presentation] 肝幹/前駆細胞表面抗原の網羅的解析と細胞移植2008

    • Author(s)
      柿沼時、他
    • Organizer
      第12回日本肝臓学会大会ワークショップ
    • Place of Presentation
      東京
    • Year and Date
      2008-10-01
    • Related Report
      2008 Annual Research Report
  • [Presentation] Analysis of cell surface proteins on hepatic stem/ progenitor cells in fetal liver2008

    • Author(s)
      Kakinuma S, et.al.
    • Organizer
      FASEB summer research conference
    • Place of Presentation
      Snowmass CO USA
    • Year and Date
      2008-08-04
    • Related Report
      2008 Annual Research Report
  • [Presentation] 胎生中期肝幹/前駆細胞表面抗原の解析と細胞移植2008

    • Author(s)
      柿沼晴、太田春彦、紙谷聡英、中内啓光
    • Organizer
      第15回肝細胞研究会(シンポジウム/肝障害と幹細胞~肝修復における幹細胞の役割)
    • Place of Presentation
      静岡
    • Year and Date
      2008-06-28
    • Related Report
      2009 Final Research Report
  • [Presentation] 肝幹/前駆細胞表面抗原のFACSによる網羅的解析2008

    • Author(s)
      柿沼晴、太田春彦、紙谷聡英、中内啓光
    • Organizer
      第44回日本肝臓学会総会
    • Place of Presentation
      松山(口演)
    • Year and Date
      2008-06-06
    • Related Report
      2009 Final Research Report
  • [Presentation] Flowcytometric analysis of cell surface molecules on mouse fetal hepatic stem/progenitor cells.2008

    • Author(s)
      Kakinuma S, Kamiya A, Ohta H, Nakauchi H
    • Organizer
      FASEB summer research conference, Liver growth, development and disease
    • Place of Presentation
      Snowmass, CO, USA
    • Related Report
      2009 Final Research Report
  • [Book] 幹細胞維持に関わるシグナル伝達-幹細胞の機能とWntシグナル 分子消化器病2010

    • Author(s)
      柿沼晴
    • Publisher
      先端医学社
    • Related Report
      2009 Final Research Report
  • [Book] 幹細胞を用いた肝再生医療の可能性iPS細胞の産業的応用技術2009

    • Author(s)
      柿沼晴
    • Publisher
      シーエムシー出版
    • Related Report
      2009 Final Research Report
  • [Book] 「iPS細胞の産業的応用技術」分著:幹細胞を用いた肝再生医療の可能性2009

    • Author(s)
      柿沼晴(山中伸弥編集)
    • Total Pages
      5
    • Publisher
      シーエムシー出版
    • Related Report
      2009 Annual Research Report
  • [Book] TCF/LEF経路を介した肝幹・前駆細胞成熟化の調節機構臨床消化器内科2008

    • Author(s)
      柿沼晴
    • Publisher
      日本メディカルセンター
    • Related Report
      2009 Final Research Report
  • [Book] Wnt-TCF/LEF経路による肝幹細胞の分化・増殖調節機構の解析(Liver Forum in Kyoto 第10回学術集会記録集)2008

    • Author(s)
      柿沼晴
    • Publisher
      メディカルトリビューン
    • Related Report
      2009 Final Research Report
  • [Book] Wnt-TCF/LEF経路による肝幹細胞の分化・増殖調節機構の解析-Liver Forum in Kyoto第10回学術集会記録集2008

    • Author(s)
      柿沼晴(分著)
    • Publisher
      メディカルトリビューン
    • Related Report
      2008 Annual Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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