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Research on transplantation of hepatic stem cells and development of experimental mouse models for hepatitis C virus

Research Project

Project/Area Number 19590752
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

CHEN Cheng-hsin  Tokyo Medical and Dental University, 医学部附属病院, 助教 (10376783)

Co-Investigator(Kenkyū-buntansha) KAKINUMA Sei  東京大学, 医科学研究所, 特任助教・客員研究員 (30372444)
SAKAMOTO Naoya  東京医科歯科大学, 医歯学総合研究科, 准教授 (10334418)
WATANABE Mamoru  東京医科歯科大学, 医歯学総合研究科, 教授 (10175127)
Co-Investigator(Renkei-kenkyūsha) SAKAMOTO Naoya  東京医科歯科大学, 医歯学総合研究科, 准教授 (10334418)
WATANABE Mamoru  東京医科歯科大学, 医歯学総合研究科, 教授 (10175127)
Project Period (FY) 2007 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords肝幹細胞 / C型肝炎ウイルス / 細胞移植 / FACS / shRNA / 肝細胞
Research Abstract

本研究において我々は、初代肝幹細胞を分離・培養し、これを利用して新規の細胞移植モデルをマウスにおいて確立すること、及びC型肝炎ウイルス(HCV)感染モデル動物の構築を行うことを目的として研究計画を遂行した。その結果、マウス肝幹細胞が高濃度に純化された画分を得る手法を確立し、その分化・増殖に制御する分子を数種類同定した。さらに、肝臓の約半分がドナー細胞によって置換される移植モデルの構築に成功した。そしてHCV感染動物に対する治療モデル系構築に成功し、研究計画を概ね達成した。

Report

(3 results)
  • 2008 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report
  • Research Products

    (47 results)

All 2009 2008 2007

All Journal Article (30 results) (of which Peer Reviewed: 27 results) Presentation (13 results) Book (4 results)

  • [Journal Article] Analyses of cell surface molecules on hepatic stem/progenitor cells in mouse fetal liver2009

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

      J Hepatol (in press)

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Two flavonoidsextracts from Glycyrrhizae radix inhibit in vitrohepatitis C virus replication2009

    • Author(s)
      Sekine-Osajima Y, Sakamoto N, Nakagawa M, Itsui Y, Tasaka M, Nishimura-Sakurai Y, Chen CH, Suda G, Mishima K, Onuki Y, Yamamoto M, Maekawa S, Enomoto N, Kanai T, Tsuchiya K and Watanabe M
    • Journal Title

      Hepatol Res 39

      Pages: 60-9

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Signaling pathway via TNFa/NFkB in intestinal epithelial cells may be directly involved in colitis-associated carcinogenesis2009

    • Author(s)
      Onizawa M, Nagaishi T, Kanai T, Nagano KI, Oshima S, Nemoto Y, Yoshioka A, Totsuka T, Okamoto R, Nakamura T, Sakamoto N, TsuchiyaK, Aoki K, Ohya K, Yagita H and Watanabe M
    • Journal Title

      Am J Physol Gastrntest Liver Physiol (Epub ahead of print)

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Sall4 regulates cell fate decision in fetal hepaticstem/progenitor cells2009

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

      Gasroenterology 139

      Pages: 1000-11

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Musashi-1 suppressesexpression of Paneth cell-specific genes inhuman intestinal epithelial cells2009

    • Author(s)
      Murayama M, Okamoto R, Tsuchiya K, Akiyama J, Nakamura T, Sakamoto N, Kanai T and Watanabe M
    • Journal Title

      Gasroenterology 44

      Pages: 173-82

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Hepatic stem/progenitor cells and stem-cell transplantation for the treatment of liver disease2009

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

      J Gasroenterology 44

      Pages: 167-72

    • NAID

      10025173601

    • Related Report
      2008 Final Research Report
  • [Journal Article] Two flavonoids extracts from Glycyrrhizae radix inhibit in vitro hepatitis C virus replication.2009

    • Author(s)
      Sekine-Osajima Y, ChenCH., et al.
    • Journal Title

      Hepatology Research 39

      Pages: 60-69

    • NAID

      10025324061

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sall4 regulates cell fate decision of fetal hepatic stem/progenitor cells2009

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

      Gastroenterology 136

      Pages: 1000-1011

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hepatic stem/progenitor eelfor the treatment of liver ds and stem-cell transplantationsease.2009

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

      J Gastroenterol 44

      Pages: 167-172

    • Related Report
      2008 Annual Research Report
  • [Journal Article] Immunosenescent colitogenicCD4(+) T cells convert to regulatory cells and Dsuppress colitis2008

    • Author(s)
      Totsuka T, Kanai T, Nemoto Y, Tomita T, Tsuchiya K, Sakamoto N, Okamoto R and Watanabe M
    • Journal Title

      Eur J Immunol 38

      Pages: 1275-86

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Systemic, but not intestinal, IL-7is essential for the persistence of chronic colitis2008

    • Author(s)
      Tomita T, Kanai T, Nemoto Y, Totsuka T, Okamoto R, Tsuchiya K, Sakamoto N and Watanabe M
    • Journal Title

      J Immunol 180

      Pages: 383-90

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Colitogenic CD4(+) effector-memory T cellsactively recirculate in chronic colitic mice2008

    • Author(s)
      Tomita T, Kanai T, Nemoto Y, Fujii T,Nozaki K, Okamoto R, Tsuchiya K, Nakamura T,Sakamoto N, Totsuka T and Watanabe M
    • Journal Title

      In flamm Bowel Dis

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Continuous generation ofcolitogenic CD4(+) T cells in persistent colitis2008

    • Author(s)
      Tomita T, Kanai T, Fujii T, Nemoto Y,Okamoto R, Tsuchiya K, Totsuka T, Sakamoto N and Watanabe M
    • Journal Title

      Eur J Immunol 38

      Pages: 1264-74

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] MyD88-dependentpathway in T cells directly modulates theexpansion of colitogenic CD4+ T cells in chroniccolitis2008

    • Author(s)
      Tomita T, Kanai T, Fujii T, Nemoto Y, Okamoto R, Tsuchiya K, Totsuka T, SakamotoN, Akira S and Watanabe M
    • Journal Title

      J Immunol 180

      Pages: 5291-9

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Development of plaque assays forhepatitis C virus-JFH1 strain and isolation ofmutants with enhanced cytopathogenicity and replication capacity2008

    • Author(s)
      Sekine-Osajima Y, Sakamoto N, MishimaK, Nakagawa M, Itsui Y, Tasaka M,Nishimura-Sakurai Y, Chen CH, Kanai T, Tsuchiya K, Wakita T, Enomoto N and Watanabe M
    • Journal Title

      Virology 371

      Pages: 71-85

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Negative feedback regulation of colitogenicCD4(+) T cells by increased granulopoiesis2008

    • Author(s)
      Nemoto Y, Kanai T, Tohda S, Totsuka T,Okamoto R, Tsuchiya K, Nakamura T, SakamotoN, Fukuda T, Miura O, Yagita H and Watanabe M
    • Journal Title

      In flamm Bowel Dis

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Effects of immunosuppressantson the progression of hepatitis C in hepatitis Cvirus-positive renal transplantation and theusefulness of interferon therapy2008

    • Author(s)
      Nanmoku K, Imaizumi R, Tojimbara T, Nakajima I, Fuchinoue S, Sakamoto N, Watanabe M and Teraoka S
    • Journal Title

      Transplant Proc 40

      Pages: 2382-5

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Prospero-relatedhomeobox 1 and liver receptor homolog 1coordinately regulate long-term proliferation ofmurine fetal hepatoblasts2008

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

      Hepatology 48

      Pages: 252-64

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Blockade of NKG2D signaling prevents the development ofmurine CD4+ T cell-mediated colitis2008

    • Author(s)
      Ito Y, Kanai T, Totsuka T, Okamoto R, Tsuchiya K, Nemoto Y, Yoshioka A, Tomita T, Nagaishi T, Sakamoto N, Sakanishi T, OkumuraK, Yagita H and Watanabe M
    • Journal Title

      Am J Physiol Gastro intest Liver Physiol 294

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] FTY720 suppresses the development of colitis in lymphoid-null mice by modulating the trafficking of colitogenic CD4+ T cells in bone marrow2008

    • Author(s)
      Fujii T, Tomita T, Kanai T, Nemoto Y,Totsuka T, Sakamoto N, Nakamura T, TsuchiyaK, Okamoto R and Watanabe M
    • Journal Title

      EurJ Immunol 38

      Pages: 3290-303

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Proteasomal degradation ofAtoh1 by aberrant Wnt signaling maintains theundifferentiated state of colon cancer2008

    • Author(s)
      Aragaki M, Tsuchiya K, Okamoto R,Yoshioka S, Nakamura T, Sakamoto N, Kanai T and Watanabe M
    • Journal Title

      Biochem Biophys Res Commun 368

      Pages: 923-9

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] TCF/LEF経路を介した肝幹・前駆細胞成熟化の調節機構2008

    • Author(s)
      柿沼晴
    • Journal Title

      臨床消化器内科 23巻13号

      Pages: 1813-1819

    • Related Report
      2008 Final Research Report
  • [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, etal.
    • Journal Title

      Hepatology 48

      Pages: 252-264

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Development of plaque assays for hepatitis C virus-JFH1 strain and isolation of mutants with enhanced cytopathogenicity and replication capacity.2008

    • Author(s)
      Sekine-Osajima Y, Sakamoto N, Chen CH, Watanabe M, et. al.
    • Journal Title

      Virology 371

      Pages: 71-85

    • Related Report
      2007 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, et. al.
    • Journal Title

      Hepatology (印刷中)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition of hepatitis C virus infection and expression in vitro and in vivo by recombinant adenovirus expressing short hairpin RNA.2008

    • Author(s)
      Sakamoto N, Chen CH, Watanabe M, et. al.
    • Journal Title

      Journal of Gastroenterology and Hepatology (印刷中)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hepatitis C virus non-structural proteins responsible for suppression of the RIG-I/Cardif-induced interferon response2007

    • Author(s)
      Tasaka M, Sakamoto N, Itakura Y,Nakagawa M, Itsui Y, Sekine-Osajima Y,Nishimura-Sakurai Y, Chen CH, Yoneyama M,Fujita T, Wakita T, Maekawa S, Enomoto N and Watanabe M
    • Journal Title

      J Gen Virol 88

      Pages: 3323-33

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Bone morphogenetic protein-7 and interferon-alpha synergistically suppresshepatitis C virus replicon2007

    • Author(s)
      Sakamoto N, Yoshimura M, Kimura T, Toyama K, Sekine-Osajima Y, Watanabe M and Muramatsu M
    • Journal Title

      Biochem Biophys Res Commun 357

      Pages: 467-73

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition of hepatitis C virus infection and expression in vitro and in vivo by recombinant adenovirus expressing short hairpin RNA2007

    • Author(s)
      Sakamoto N, Tanabe Y, Yokota T, Satoh K, Sekine-Osajima Y, Nakagawa M, Itsui Y, Tasaka M, Sakurai Y, Chen CH, Yano M, Ohkoshi S,Aoyagi Y, Maekawa S, Enomoto N, Kohara M and Watanabe M
    • Journal Title

      J Gastroenterol Hepatol

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Hepatitis C virus non-structural proteins responsible for suppression of the RIG-I/Cardif-induced interferon response.2007

    • Author(s)
      Tasaka M, Sakamoto N, Chen CH, Watanabe M, et. al.
    • Journal Title

      Journal of General Virology 88

      Pages: 3323-3333

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [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
      JDDW2008(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
      2008 Final Research Report
  • [Presentation] Analysis of cell surface proteins on hepatic stem/progenitorcells 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
      2008 Final Research Report
  • [Presentation] 3cmを超える肝細胞癌に対する当科の治療方法と成績2008

    • Author(s)
      陳正新、坂本直哉、井津井康浩、中川美奈、櫻井幸、須田剛生、山本満千、小貫優子、三島果子、渡辺守
    • Organizer
      第44回日本肝臓学会総会
    • Place of Presentation
      松山
    • Year and Date
      2008-06-06
    • Related Report
      2008 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
      2008 Final Research Report
  • [Presentation] 3cmを超える肝細胞癌に対する当科の治療方法と成績2008

    • Author(s)
      陳 正新, 他
    • Organizer
      第4 4回日本肝臓学会総会
    • Place of Presentation
      愛媛県県民文化会蔀
    • Year and Date
      2008-06-05
    • Related Report
      2008 Annual Research Report
  • [Presentation] Flowcytometric analysis of cell surfacemolecules on mouse fetal hepaticstem/progenitor cells2008

    • 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
      2008 Final Research Report
  • [Presentation] ラジオ波熱凝固療法における第二世代超音波造影剤の有用性2007

    • Author(s)
      陳正新、坂本直哉、井津井康浩、中川美奈、筬島裕子、田坂めぐみ、櫻井幸、渡辺守
    • Organizer
      JDDW2007(第10回日本肝臓学会大会)
    • Place of Presentation
      神戸
    • Year and Date
      2007-10-18
    • Related Report
      2008 Final Research Report
  • [Presentation] TCF/LEF活性化による肝幹/前駆細胞の分化・増殖の調節2007

    • Author(s)
      柿沼晴、紙谷聡英、中内啓光
    • Organizer
      JDDW2007(第10回日本肝臓学会大会ワークショップ/肝の再生医学・医療/人工肝臓の現状と展望)
    • Place of Presentation
      神戸
    • Year and Date
      2007-10-18
    • Related Report
      2008 Final Research Report
  • [Presentation] TCF/LEF活性化による肝幹/前駆細胞の分化・増殖の調節2007

    • Author(s)
      柿沼 晴、他
    • Organizer
      第11回日本肝臓学会大会ワークショップ
    • Place of Presentation
      神戸
    • Year and Date
      2007-10-18
    • Related Report
      2007 Annual Research Report
  • [Presentation] 肝幹/前駆細胞におけるTCF/LEF活性化2007

    • Author(s)
      柿沼晴、紙谷聡英、中内啓光
    • Organizer
      第14回肝細胞研究会(ワークショップ/肝幹細胞研究の現況と展望)
    • Place of Presentation
      鹿児島
    • Year and Date
      2007-06-23
    • Related Report
      2008 Final Research Report
  • [Presentation] Wnt/TCF signaling pathwayを介した肝前駆細胞成熟化の調節機構2007

    • Author(s)
      柿沼晴、紙谷聡英、中内啓光
    • Organizer
      第43回日本肝臓学会総会(ワークショップ/肝再生とその臨床応用)
    • Place of Presentation
      東京
    • Year and Date
      2007-05-31
    • Related Report
      2008 Final Research Report
  • [Presentation] 当科における高齢肝細胞癌患者に対するラジオ波熱凝固療法の治療成績2007

    • Author(s)
      陳正新、坂本直哉、渡辺守
    • Organizer
      第43回日本肝臓学会総会
    • Place of Presentation
      東京
    • Year and Date
      2007-05-31
    • Related Report
      2008 Final Research Report
  • [Book] 幹細胞を用いた肝再生医療の可能性2009

    • Author(s)
      柿沼晴
    • Publisher
      iPS細胞の産業的応用技術(シーエムシー出版)(印刷中)
    • Related Report
      2008 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2008

    • Author(s)
      柿沼晴
    • Publisher
      Liver Forum in Kyoto第10回学術集会記録集(メディカルトリビューン)
    • Related Report
      2008 Final Research Report
  • [Book] 幹細胞-肝幹細胞を用いた細胞移植の可能性2007

    • Author(s)
      柿沼晴
    • Publisher
      再生医療技術の最前線(シーエムシー出版)
    • Related Report
      2008 Final Research Report
  • [Book] 再生医療技術の最前線:幹細胞-肝幹細胞を用いた細胞移植の可能性2007

    • Author(s)
      柿沼 晴(岡野光夫他監修)分著
    • Publisher
      シーエムシー出版
    • Related Report
      2007 Annual Research Report

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Published: 2007-04-01   Modified: 2016-04-21  

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