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Pathophysiological Roles of Mesenchymal Stem Cells and Hematopoietic Stem Cells in Hepatic Fibrosis

Research Project

Project/Area Number 22659152
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Gastroenterology
Research InstitutionTokai University

Principal Investigator

INAGAKI Yutaka  東海大学, 医学部, 教授 (80193548)

Co-Investigator(Renkei-kenkyūsha) MATSUZAKI Yumi  慶応義塾大学, 医学部, 准教授 (50338183)
HIGASHIYAMA Reiichi  東海大学, 医学部, 奨励研究員 (80459495)
Project Period (FY) 2010 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥3,260,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2010: ¥1,700,000 (Direct Cost: ¥1,700,000)
Keywords肝線維化 / 骨髄幹細胞 / 骨髄 / 造血幹細胞 / 間葉系幹細胞
Research Abstract

There are two types of stem cells, hematopoietic stem cells(HSC) and mesenchymal stem cells(MSC), present in bone marrow(BM). While HSC have been well characterized and applied for BM transplantation, little is known about the physiological roles of MSC. In this study, we have revealed that hematopoietic cells derived from HSC migrate into fibrotic liver and contribute the regression of fibrosis by expressing collagenases. In contrast, MSC or its derivatives are not mobilized from BM into fibrotic liver tissue during hepatic fibrogenesis.

Report

(3 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • Research Products

    (43 results)

All 2012 2011 2010 Other

All Journal Article (9 results) (of which Peer Reviewed: 6 results) Presentation (27 results) Book (2 results) Remarks (2 results) Patent(Industrial Property Rights) (3 results)

  • [Journal Article] Interplay between bone marrow and liver in the pathogenesis of hepatic fibrosis2012

    • Author(s)
      Inagaki Y, Higashiyama R
    • Journal Title

      Hepatol Res

      Volume: 42 Pages: 543-548

    • NAID

      10031144268

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Novel anti-fibrotic modalities for liver fibrosis : Molecular targeting and regenerative medicine in fibrosis therapy2012

    • Author(s)
      Inagaki Y, Higashiyama R, Higashi K
    • Journal Title

      J Gastroenterol Hepatol

      Volume: 27 Pages: 85-88

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] A novel small compound that promotes nuclear translocation of YB-1 ameliorates experimental hepatic fibrosis in mice2011

    • Author(s)
      Higashi K, Tomigahara Y, Inagaki Y, 他6名
    • Journal Title

      J Biol Chem

      Volume: 286 Pages: 4485-4492

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Differential contribution of dermal resident and bone marrow-derived cells to collagen production during wound healing and fibrogenesis in mice2011

    • Author(s)
      Higashiyama R, Nakao S, Inagaki Y, 他9名
    • Journal Title

      J Invest Dermatol

      Volume: 131 Pages: 529-536

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] 創傷治癒ならびに皮膚線維化過程における骨髄由来細胞の役割2011

    • Author(s)
      稲垣豊
    • Journal Title

      日本皮膚科学会雑誌

      Volume: 121 Pages: 3185-3187

    • NAID

      10031165157

    • Related Report
      2011 Annual Research Report
  • [Journal Article] A novel small compound that promotes nuclear translocation of YB-1 ameliorates experimental hepatic fibrosis in mice.2011

    • Author(s)
      Kiyoshi Higashi
    • Journal Title

      Journal of Biological Chemistry

      Volume: 286 Pages: 4485-4492

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Differential contribution of dermal resident and bone marrow-derived cells to collagen production during wound healing and fibrogenesis in mice.2011

    • Author(s)
      Reiichi Higashiyama
    • Journal Title

      Journal of Investigative Dermatology

      Volume: 131 Pages: 529-536

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] TGF-β/Smadシグナルを標的とした肝線維症の治療戦略2010

    • Author(s)
      稲垣豊
    • Journal Title

      瘢痕・ケロイド治療ジャーナル

      Volume: 4 Pages: 35-39

    • Related Report
      2010 Annual Research Report
  • [Journal Article] 臓器線維症の病態と治療戦略2010

    • Author(s)
      稲垣豊
    • Journal Title

      十全医学会雑誌

      Volume: 119 Pages: 56-57

    • NAID

      10027445155

    • Related Report
      2010 Annual Research Report
  • [Presentation] 骨髄造血幹細胞ならびに間葉系幹細胞による肝線維化の病態形成2011

    • Author(s)
      中尾祥絵
    • Organizer
      第25回肝類洞壁細胞研究会学術集会
    • Place of Presentation
      東京ガーデンパレス(東京)
    • Year and Date
      2011-12-18
    • Related Report
      2011 Annual Research Report
  • [Presentation] 骨髄細胞に由来する新たな肝線維化改善・再生促進因子の同定と臨床応用2011

    • Author(s)
      福光寛
    • Organizer
      第25回肝類洞壁細胞研究会学術集会
    • Place of Presentation
      東京ガーデンパレス(東京)
    • Year and Date
      2011-12-18
    • Related Report
      2011 Annual Research Report
  • [Presentation] 肝細胞増殖因子HGFが有する肝癌細胞増殖抑制作用の解析2011

    • Author(s)
      瀧澤友里
    • Organizer
      第25回肝類洞壁細胞研究会学術集会
    • Place of Presentation
      東京ガーデンパレス(東京)
    • Year and Date
      2011-12-18
    • Related Report
      2011 Annual Research Report
  • [Presentation] Notch/Jagged-1 signal modulates pathophysiological correlation between fibrogenesis and regeneration in murine liver2011

    • Author(s)
      Kenichiro Mikami
    • Organizer
      62th Annual Meeting of the American Association for the Study of Liver Diseases
    • Place of Presentation
      Moscone West (San Francisco, CA)
    • Year and Date
      2011-11-07
    • Related Report
      2011 Annual Research Report
  • [Presentation] Anti-fibrotic modalities for liver fibrosis. From Stem Cells to Global Health2011

    • Author(s)
      Inagaki Y
    • Organizer
      6th International Symposium on ALPD and Cirrhosis
    • Place of Presentation
      Fukuoka, Japan
    • Year and Date
      2011-10-21
    • Related Report
      2011 Final Research Report
  • [Presentation] Anti-fibrotic modalities for liver fibrosis2011

    • Author(s)
      Yutaka Inagaki
    • Organizer
      6th International Symposium on ALPD and Cirrhosis
    • Place of Presentation
      Fukuoka Convention Center (Fukuoka, Japan)(招待講演)
    • Year and Date
      2011-10-21
    • Related Report
      2011 Annual Research Report
  • [Presentation] 肝線維化と肝再生の病態連繋におけるNotch/Jagged-1シグナルの関与2011

    • Author(s)
      三上健一郎
    • Organizer
      第18回肝細胞研究会
    • Place of Presentation
      東京ガーデンパレス(東京)
    • Year and Date
      2011-06-24
    • Related Report
      2011 Annual Research Report
  • [Presentation] 酸化ストレスに起因する肝細胞傷害と肝線維化進展の高感度検出系の確立2011

    • Author(s)
      皆川香織
    • Organizer
      第43回日本結合組織学会学術大会第58回マトリックス研究会大会合同学術集会
    • Place of Presentation
      別府ビーコンプラザ(大分)
    • Year and Date
      2011-06-11
    • Related Report
      2011 Annual Research Report
  • [Presentation] 骨髄造血幹細胞ならびに間葉系幹細胞による肝線維症の病態形成2011

    • Author(s)
      中尾祥絵
    • Organizer
      第43回日本結合組織学会学術大会第58回マトリックス研究会大会合同学術集会
    • Place of Presentation
      別府ビーコンプラザ(大分)
    • Year and Date
      2011-06-11
    • Related Report
      2011 Annual Research Report
  • [Presentation] Pathogenesis of hepatic fibrosis. Symposium 4 : Hepatic Fibrosis2011

    • Author(s)
      Inagaki Y
    • Organizer
      17th Annual Meeting of the Korean Association for the Study of the Liver.
    • Place of Presentation
      Seoul, Korea
    • Year and Date
      2011-06-10
    • Related Report
      2011 Final Research Report
  • [Presentation] Pathogenesis of hepatic fibrosis, update2011

    • Author(s)
      Yutaka Inagaki
    • Organizer
      17th Annual Meeting of the Korean Association for the Study of the Liver
    • Place of Presentation
      Sheraton Grande Walkerhill Hotel (Seoul, Korea)(招待講演)
    • Year and Date
      2011-06-10
    • Related Report
      2011 Annual Research Report
  • [Presentation] 肝線維化と肝再生の病態連繋におけるNotch/Jagged-1シグナルの関与2011

    • Author(s)
      三上健一郎
    • Organizer
      第47回日本肝臓学会総会
    • Place of Presentation
      ホテルグランパシフィックLE DAIBA(東京)
    • Year and Date
      2011-06-03
    • Related Report
      2011 Annual Research Report
  • [Presentation] Notch/Jagged-1 signal modulates pathophysiological correlation between fibrogenesis and regeneration in murine liver.2011

    • Author(s)
      Yutaka Inagaki
    • Organizer
      American Association for the Study of Liver Diseases, Basic Research Single Topic Conference "Stem Cells in Liver Diseases and Cancer"
    • Place of Presentation
      Atlanta, GA
    • Year and Date
      2011-03-19
    • Related Report
      2010 Annual Research Report
  • [Presentation] Jagged-1を介した肝線維化と再生の病態連繋2011

    • Author(s)
      三上健一郎
    • Organizer
      第10回日本再生医療学会総会
    • Place of Presentation
      東京
    • Year and Date
      2011-03-01
    • Related Report
      2010 Annual Research Report
  • [Presentation] 胆汁うっ滞型肝線維症におけるコラーゲン産生細胞の起源と初期動態2010

    • Author(s)
      茂呂忠
    • Organizer
      第24回肝類洞壁細胞研究会学術大会
    • Place of Presentation
      福島
    • Year and Date
      2010-11-27
    • Related Report
      2010 Annual Research Report
  • [Presentation] Molecular mechanisms of hepatic stellate cell activation2010

    • Author(s)
      Inagaki Y
    • Organizer
      9th Japan Society of Hepatology Single Topic Conference : NASH 2010
    • Place of Presentation
      Tokyo, Japan
    • Year and Date
      2010-11-19
    • Related Report
      2011 Final Research Report
  • [Presentation] Molecular mechanisms of hepatic stellate cell activation.2010

    • Author(s)
      Yutaka Inagaki
    • Organizer
      9th Japan Society of Hepatology Single Topic Conference "NASH 2010"
    • Place of Presentation
      Tokyo, Japan.
    • Year and Date
      2010-11-19
    • Related Report
      2010 Annual Research Report
  • [Presentation] Jagged-1を介した肝線維化と再生の病態連繋2010

    • Author(s)
      三上健一郎
    • Organizer
      第14回日本肝臓学会大会
    • Place of Presentation
      横浜
    • Year and Date
      2010-10-14
    • Related Report
      2010 Annual Research Report
  • [Presentation] Notch/Jagged-1 signal modulates pathophysiological correlation between fibrogenesis and regeneration in murine liver.2010

    • Author(s)
      Kenichiro Mikami
    • Organizer
      1st Japanese Society of Gastroenterology International Topic Conference : Stem Cells in Digestive Organs
    • Place of Presentation
      Kamakura, Japan
    • Year and Date
      2010-09-25
    • Related Report
      2010 Annual Research Report
  • [Presentation] Matrix metalloproteinase (MMP)-13 enhances migration of bone marrow-derived cells and contributes to the repair of experimental liver fibrosis.2010

    • Author(s)
      Reiichi Higashiyama
    • Organizer
      15th International Symposium on Cells of the Hepatic Sinusoid
    • Place of Presentation
      Pasadena, CA
    • Year and Date
      2010-08-31
    • Related Report
      2010 Annual Research Report
  • [Presentation] マウス胆汁うっ滞型肝線維症に胆管上皮細胞の上皮間葉移行は関与するか2010

    • Author(s)
      茂呂忠
    • Organizer
      第42回日本結合組織学会学術大会・第57回マトリックス研究会大会合同学術集会
    • Place of Presentation
      秋田
    • Year and Date
      2010-08-19
    • Related Report
      2010 Annual Research Report
  • [Presentation] Jagged-1を介した肝線維化と再生の病態連繋2010

    • Author(s)
      三上健一郎
    • Organizer
      第42回日本結合組織学会学術大会・第57回マトリックス研究会大会合同学術集会
    • Place of Presentation
      秋田
    • Year and Date
      2010-08-19
    • Related Report
      2010 Annual Research Report
  • [Presentation] 皮膚創傷治癒ならびに線維化過程における骨髄由来細胞のコラーゲン合成への関与の相違2010

    • Author(s)
      中尾祥絵
    • Organizer
      第42回日本結合組織学会学術大会・第57回マトリックス研究会大会合同学術集会
    • Place of Presentation
      秋田
    • Year and Date
      2010-08-19
    • Related Report
      2010 Annual Research Report
  • [Presentation] 肝線維化と再生の病態連繋における骨髄と末梢の臓器相関.シンポジウム2「肝幹細胞と肝再生」2010

    • Author(s)
      稲垣豊、東山礼一、三上健一郎
    • Organizer
      第17回肝細胞研究会
    • Place of Presentation
      秋田アトリオン(秋田)
    • Year and Date
      2010-06-19
    • Related Report
      2011 Final Research Report
  • [Presentation] 肝線維化と再生の病態連繋における骨髄と末梢の臓器相関2010

    • Author(s)
      稲垣豊
    • Organizer
      第17回肝細胞研究会
    • Place of Presentation
      秋田
    • Year and Date
      2010-06-19
    • Related Report
      2010 Annual Research Report
  • [Presentation] Matrix metalloproteinase(MMP)-13による線維化改善と類洞構造の修復を介した肝再生治療戦略.移植・再生医療ワークショップ2「肝再生医学-臨床応用を目指した研究の新展開」2010

    • Author(s)
      東山礼一、三上健一郎、稲垣豊
    • Organizer
      第46回日本肝臓学会総会
    • Place of Presentation
      ホテルメトロポリタン山形(山形)
    • Year and Date
      2010-05-28
    • Related Report
      2011 Final Research Report
  • [Presentation] Matrix metalloproteinase (MMP)-13による線維化改善と類洞構造の修復を介した肝再生治療戦略2010

    • Author(s)
      東山礼一
    • Organizer
      第46回日本肝臓学会総会
    • Place of Presentation
      山形
    • Year and Date
      2010-05-28
    • Related Report
      2010 Annual Research Report
  • [Book] 肝線維化病態に対する分子形態学的アプローチ.病気の分子形態学.(日本臨床分子形態学会編)2011

    • Author(s)
      稲垣豊、東山礼一、茂呂忠、中尾祥絵、皆川香織、三上健一郎
    • Publisher
      学際企画
    • Related Report
      2011 Final Research Report
  • [Book] 肝線維化病態に対する分子形態学的アプローチ.病気の分子形態学(日本臨床分子形熊学会編)2011

    • Author(s)
      稲垣豊
    • Publisher
      学際企画
    • Related Report
      2011 Annual Research Report
  • [Remarks]

    • URL

      http://www.med.u-tokai.ac.jp/daigakuin/pdf/inagaki.pdf

    • Related Report
      2011 Final Research Report
  • [Remarks]

    • URL

      http://www.med.u-tokai.ac.jp/daieakuin/pdf/inagaki.pdf

    • Related Report
      2011 Annual Research Report
  • [Patent(Industrial Property Rights)] 肝臓線維化抑制剤2011

    • Inventor(s)
      稲垣豊、茂呂忠
    • Industrial Property Rights Holder
      学校法人東海大学、株式会社ミノファーゲン製薬
    • Industrial Property Number
      2011-250746
    • Filing Date
      2011-11-16
    • Related Report
      2011 Final Research Report
  • [Patent(Industrial Property Rights)] 肝臓線維化抑制剤2011

    • Inventor(s)
      稲垣豊, 茂呂忠
    • Industrial Property Rights Holder
      学校法人東海大学、株式会社ミノファーゲン製薬
    • Industrial Property Number
      2011-250746
    • Filing Date
      2011-11-16
    • Related Report
      2011 Annual Research Report
  • [Patent(Industrial Property Rights)] 生体組織再生を促進させる薬剤を製造するための加工細胞2010

    • Inventor(s)
      稲垣豊、東山礼一東清史、斎藤幸一
    • Industrial Property Rights Holder
      学校法人東海大学、住友化学工業株式会社
    • Industrial Property Number
      2010-122501
    • Filing Date
      2010-05-28
    • Related Report
      2011 Final Research Report

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Published: 2010-08-23   Modified: 2016-04-21  

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