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The analysis of small bone marrow drived liver repair cell

Research Project

Project/Area Number 24590978
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Gastroenterology
Research InstitutionYamaguchi University

Principal Investigator

YAMAMOTO Naoki  山口大学, 大学教育機構, 講師 (90448283)

Co-Investigator(Kenkyū-buntansha) TERAI Shuji  新潟大学, 医歯学系研究科, 教授 (00332809)
TAKAMI Taro  山口大学, 大学院医学系研究科, 講師 (60511251)
FUJISAWA Koichi  山口大学, 大学院医学系研究科, 助教 (00448284)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords再生医療 / 電子顕微鏡 / 肝線維化 / 骨髄細胞 / 幹細胞 / 免疫電顕 / CCL4モデル / EpCAM / CCl4モデル / AutoMACS / stem cell
Outline of Final Research Achievements

We developed the GFP/CCl4 model which monitor the GFP-positive bone marrow cell (BMC) repopulated under CCl4 induced liver cirrhosis mice.We found two kinds of GFP positive BMCs in recipient cirrhosis liver using IEM method. One group of GFP positive BMCs was similar to hepatocyte in size(15-30um) and located around fiber(MMP9 positive cell).The other group cells were small size (2-5microum) and located in destructive area(A6 positive cell, Liv2 positive cell). And EpCAM positive cells were included. These cells were circular forms and had high N/C ratio and smaller than hepatocyte. We separated EpCAM-positive and EpCAM-negative cells and then transplanted these cells into a continuous liver damaged model(CCl4 model). At 4 weeks after BMC transplantation, the ratio of liver fibrosis in EpCAM-negative cells injected liver was decreased better than EpCAM-positive cells.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (41 results)

All 2015 2014 2013 2012 2011 Other

All Journal Article (16 results) (of which Peer Reviewed: 16 results,  Open Access: 1 results,  Acknowledgement Compliant: 2 results) Presentation (22 results) Remarks (2 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Enhanced survival of mice infused with bone marrow-derived as compared with adipose-derived mesenchymal stem cells.2014

    • Author(s)
      Shiratsuki S, Terai S, Murata Y, Takami T, Yamamoto N, Fujisawa K, Burganova G, Quintanilha LF, Sakaida I.
    • Journal Title

      Hepatol Res

      Volume: - Issue: 13 Pages: 1353-1359

    • DOI

      10.1111/hepr.12507

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Status and prospects of liver cirrhosis treatment by using bone marrow-derived cells and mesenchymal cells.2014

    • Author(s)
      Terai S, Takami T, Yamamoto N, Fujisawa K, Ishikawa T, Urata Y, Tanimoto H, Iwamoto T, Mizunaga Y, Matsuda T, Oono T, Marumoto M, Burganova G, Fernando Quintanilha L, Hidaka I, Marumoto Y, Saeki I, Uchida K, Yamasaki T, Tani K, Taura Y, Fujii Y, Nishina H, Okita K, Sakaida I.
    • Journal Title

      Tissue Eng Part B Rev

      Volume: 20(3) Issue: 3 Pages: 206-210

    • DOI

      10.1089/ten.teb.2013.0527

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Canine mesenchymal stem cells show antioxidant properties against thioacetamide-induced liver injury in vitro and in vivo.2013

    • Author(s)
      Quintanilha LF, Takami T, Hirose Y, Fujisawa K, Murata Y, Yamamoto N, Goldenberg RC, Terai S, Sakaida I.
    • Journal Title

      Hepatol Res.

      Volume: - Issue: 10

    • DOI

      10.1111/hepr.12204

    • Related Report
      2014 Annual Research Report 2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Serum transferrin as a predictor of prognosis for hepatic arterial infusion chemotherapy in advanced hepatocellular carcinoma.2013

    • Author(s)
      Zaitu J
    • Journal Title

      Hepatol Res

      Volume: Apr 22 Issue: 5 Pages: 481-90

    • DOI

      10.1111/hepr.12141

    • Related Report
      2014 Annual Research Report 2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Improvement of liver fibrosis by infusion of cultured cells derived from human bone marrow.2013

    • Author(s)
      Tanimoto H, Terai S, Taro T, Murata Y, Fujisawa K, Yamamoto N, Sakaida I.
    • Journal Title

      Cell Tissue Res.

      Volume: 354(3) Issue: 3 Pages: 717-28

    • DOI

      10.1007/s00441-013-1727-2

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Bone-marrow-derived cells cultured in serum-free medium reduce liver fibrosis and improve liver function in carbon-tetrachloride-treated cirrhotic mice.2013

    • Author(s)
      Iwamoto T, Terai S, Hisanaga T, Takami T, Yamamoto N, Watanabe S, Sakaida I.
    • Journal Title

      Cell Tissue Res.

      Volume: 351(3) Issue: 3 Pages: 487-95

    • DOI

      10.1007/s00441-012-1528-z

    • Related Report
      2013 Research-status Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Bortezomib induces tumor-specific cell death and growth inhibition in hepatocellular carcinoma and improves liver fibrosis.2013

    • Author(s)
      Saeki I, Terai S, Fujisawa K, Takami T, Yamamoto N, Matsumoto T, Hirose Y, Murata Y, Yamasaki T, Sakaida I.
    • Journal Title

      J Gastroenterol.

      Volume: 48(6) Issue: 6 Pages: 738-50

    • DOI

      10.1007/s00535-012-0675-z

    • NAID

      10031184064

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Bortezomib induces tumor-specific cell death and growth inhibition in hepatocellular carcinoma and improves liver fibrosis.2012

    • Author(s)
      Saeki I
    • Journal Title

      J Gastroenterol.

      Volume: Sep 26 Pages: 1-13

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Advanced therapies using autologous bone marrow cells for chronic liver disease.2012

    • Author(s)
      Takami T
    • Journal Title

      Discov Med

      Volume: 14(74) Pages: 7-12

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Granulocyte colony-stimulating factor and interleukin-1β are important cytokines in repair of the cirrhotic liver after bone marrow cell infusion: comparison of humans and model mice.2012

    • Author(s)
      Mizunaga Y
    • Journal Title

      Cell Transplant.

      Volume: 21(11) Issue: 11 Pages: 2363-2375

    • DOI

      10.3727/096368912x638856

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Timeline for development of autologous bone marrow infusion (ABMi) therapy and perspective for future stem cell therapy.2012

    • Author(s)
      Terai S
    • Journal Title

      J Gastroenterol.

      Volume: 47(5) Issue: 5 Pages: 491-497

    • DOI

      10.1007/s00535-012-0580-5

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Stem cell therapy in chronic liver disease.2012

    • Author(s)
      Takami T
    • Journal Title

      Curr Opin Gastroenterol

      Volume: 28(3) Issue: 3 Pages: 203-208

    • DOI

      10.1097/mog.0b013e3283521d6a

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Autologous bone marrow cell infusions suppress tumor initiation in hepatocarcinogenic mice with liver cirrhosis.2012

    • Author(s)
      Maeda M
    • Journal Title

      J Gastroenterol Hepatol.

      Volume: Mar;27 Suppl 2 Issue: s2 Pages: 104-111

    • DOI

      10.1111/j.1440-1746.2011.07016.x

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Therapeutic potential of canine bone marrow stromal cells (BMSCs) in the carbon tetrachloride (CCl4) induced chronic liver dysfunction mouse model.2012

    • Author(s)
      Haraguchi T
    • Journal Title

      J Vet Med Sci.

      Volume: 74(5) Pages: 607-11

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Matrix metalloproteinases (MMPs) activity in cultured canine bone marrow stromal cells (BMSCs).2012

    • Author(s)
      Haraguchi T
    • Journal Title

      J Vet Med Sci.

      Volume: 74(5) Pages: 633-6

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Splenectomy enhances the anti-fibrotic effect of bone marrow cell infusion and improves liver function in cirrhotic mice and patients2011

    • Author(s)
      Iwamoto T
    • Journal Title

      J Gastroenterol

      Volume: 47(3) Issue: 3 Pages: 300-312

    • DOI

      10.1007/s00535-011-0486-7

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] 肝臓線維化における骨髄由来肝臓修復細胞の特徴2015

    • Author(s)
      山本 直樹 高見 太郎 藤澤 浩一 寺井 崇二 坂井田 功
    • Organizer
      第14回日本再生医療学会総会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2015-03-19 – 2015-03-21
    • Related Report
      2014 Annual Research Report
  • [Presentation] 培養骨髄間葉系幹細胞投与による肝臓再生メカニズムの解明2015

    • Author(s)
      高見 太郎 藤澤 浩一 山本 直樹 寺井 崇二 坂井田 功
    • Organizer
      第14回日本再生医療学会総会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2015-03-19 – 2015-03-21
    • Related Report
      2014 Annual Research Report
  • [Presentation] Less invasive liver regeneration therapy for liver cirrhosis using cultured autologous bone marrow-derived mesenchymal stem cells with redox-regulatory capacity.2014

    • Author(s)
      Takami Taro Shuji Terai Isao Sakaida
    • Organizer
      The Liver Meeting 2014, AASLD
    • Place of Presentation
      John B. Hynes Veterans Memorial Convention Center(Boston USA)
    • Year and Date
      2014-11-07 – 2014-11-11
    • Related Report
      2014 Annual Research Report
  • [Presentation] New canine liver cirrhotic model to develop a less invasive regeneration therapy using cultured autologous bone marrow-derived cells2014

    • Author(s)
      Takashi Matsuda, Taro Takami, Tsuyoshi Ishikawa, Naoki Yamamoto, Shuji Terai, Isao Sakaida
    • Organizer
      The Liver Meeting 2014, AASLD
    • Place of Presentation
      John B. Hynes Veterans Memorial Convention Center(Boston USA)
    • Year and Date
      2014-11-07 – 2014-11-11
    • Related Report
      2014 Annual Research Report
  • [Presentation] Our regeneration therapies using autologous bone marrow cells for liver cirrhosis.2014

    • Author(s)
      Taro Takami, Shuji Terai, Bruno Diaz Paredes, Luiz Fernando Quintanilha, Koichi Fujisawa, Naoki Yamamoto, Isao Sakaida
    • Organizer
      JDDW 2014 International Session (Symposium)
    • Place of Presentation
      神戸国際会議場(兵庫県神戸市)
    • Year and Date
      2014-10-23 – 2014-10-26
    • Related Report
      2014 Annual Research Report
  • [Presentation] 培養自己骨髄間葉系幹細胞投与の安全性・有効性および投与経路評価のためのイヌ肝線維化モデル2014

    • Author(s)
      松田 崇史、高見 太郎、石川 剛、山本 直樹、寺井 崇二、坂井田 功
    • Organizer
      第50回日本肝臓学会総会
    • Place of Presentation
      ホテルニューオータニ (東京)
    • Year and Date
      2014-05-29 – 2014-05-30
    • Related Report
      2014 Annual Research Report
  • [Presentation] 次世代型経口鉄キレート剤は再発予防剤およびソラフェニブの副作用軽減剤となりうる2014

    • Author(s)
      山本 直樹、山崎 隆弘、佐伯 一成、高見 太郎、藤澤 浩一、内田 耕一、寺井 崇二、 坂井田 功
    • Organizer
      第50回日本肝臓学会総会
    • Place of Presentation
      ホテルニューオータニ (東京)
    • Year and Date
      2014-05-29 – 2014-05-30
    • Related Report
      2014 Annual Research Report
  • [Presentation] 骨髄由来及び脂肪組織由来間葉系幹細胞(BMSC・ASC)における生物学的特性の差異に関する検討2014

    • Author(s)
      白築 祥吾, 寺井 崇二, 村田 泰彦, 松田 崇史 石川 剛, 高見 太郎, 山本 直樹, 坂井田 功
    • Organizer
      第50回日本肝臓学会総会
    • Place of Presentation
      ホテルニューオータニ (東京)
    • Year and Date
      2014-05-29 – 2014-05-30
    • Related Report
      2014 Annual Research Report
  • [Presentation] 自己骨髄細胞による肝臓再生療法の取り組み2013

    • Author(s)
      高見 太郎
    • Organizer
      第40回日本肝臓学会西部会
    • Place of Presentation
      長良川国際会議場(岐阜)
    • Related Report
      2013 Research-status Report
  • [Presentation] The new oral iron chelator, Deferasirox, is the new drug to prevent Liver Fibrosis and Hepatocarcinogenesis2013

    • Author(s)
      Naoki Yamamoto
    • Organizer
      AASLD's 64th Annual Liver Meeting 2013
    • Place of Presentation
      Washington Convention Center(Washington USA)
    • Related Report
      2013 Research-status Report
  • [Presentation] Basic studies for a less invasive liver regeneration therapy for liver cirrhosis using cultured autologous bone marrow-derived mesenchymal stem cells with stabilization of redox homeostasis.2013

    • Author(s)
      Taro Takami
    • Organizer
      AASLD's 64th Annual Liver Meeting 2013
    • Place of Presentation
      Washington Convention Center(Washington USA)
    • Related Report
      2013 Research-status Report
  • [Presentation] The new oral iron chelator prevents liver fibrosis and preneoplastic lesions in liver cancer and liver cirrhosis model2013

    • Author(s)
      Naoki Yamamoto
    • Organizer
      The 21st United European Gastroenterology Week (UEGW /Gastro 2013 )
    • Place of Presentation
      ICC, Berlin (Germany)
    • Related Report
      2013 Research-status Report
  • [Presentation] Basic studies for a less invasive liver regeneration therapy for liver cirrhosis using cultured autologous bone marrow-derived mesenchymal stem cells with stabilization of redox homeostasis.2013

    • Author(s)
      Taro Takami
    • Organizer
      The 20th Annual Meeting of the Japanese Society for the Research of Hepatic Cells (20th JSRH)
    • Place of Presentation
      大阪国際会議場(大阪)
    • Related Report
      2013 Research-status Report
  • [Presentation] ヒト骨髄由来および脂肪組織由来間葉系幹細胞における組織因子およびIL-8の発現検討2013

    • Author(s)
      高見 太郎
    • Organizer
      第49回日本肝臓学会総会
    • Place of Presentation
      京王プラザホテル(東京)
    • Related Report
      2013 Research-status Report
  • [Presentation] 骨髄間葉系細胞による低侵襲肝修復療法のための基礎研究2012

    • Author(s)
      高見 太郎
    • Organizer
      第26回肝類洞壁細胞研究会学術集会
    • Place of Presentation
      ANAクラウンプラザホテル宇部(山口)
    • Related Report
      2012 Research-status Report
  • [Presentation] 鉄キレート剤による肝線維化・肝発癌抑制効果の検討2012

    • Author(s)
      山本 直樹
    • Organizer
      第26回肝類洞壁細胞研究会学術集会
    • Place of Presentation
      ANAクラウンプラザホテル宇部(山口)
    • Related Report
      2012 Research-status Report
  • [Presentation] Dipeptidyl peptidase-4(DPP IV) inhibitor prevents liver fibrosis and preneoplastic lesion in rat liver cirrhosis induced by a choline-deficient L-amino acid-defined diet2012

    • Author(s)
      Yamamoto Naoki
    • Organizer
      United European Gastroenterology Week (UEGW /Gastro 2012 )
    • Place of Presentation
      Amsterdam, Netherlands
    • Related Report
      2012 Research-status Report
  • [Presentation] 骨髄細胞投与による酸化ストレス制御を介した肝発癌抑制メカニズムの解明2012

    • Author(s)
      高見 太郎
    • Organizer
      第20回JDDW2012
    • Place of Presentation
      神戸国際会議場(神戸)
    • Related Report
      2012 Research-status Report
  • [Presentation] 肝硬変に対する有機-無機・ナノハイブリッドシステムによる低侵襲再生修復療法の開発のための基礎研究2012

    • Author(s)
      高見 太郎
    • Organizer
      第11回日本再生医療学会総会
    • Place of Presentation
      バシフィコ横浜(横浜)
    • Related Report
      2012 Research-status Report
  • [Presentation] 肝硬変に対する自己骨髄細胞投与(ABMi)療法における肝発癌への影響の基礎的検討2012

    • Author(s)
      高見 太郎
    • Organizer
      第11回日本再生医療学会総会
    • Place of Presentation
      バシフィコ横浜(横浜)
    • Related Report
      2012 Research-status Report
  • [Presentation] Bone marrow cell infusions suppress hepatocarcinogenesis in N-nitrosodiethylamine-and carbon tetrachloride-induced hepatocarcinogenic mice with liver cirrhosis2012

    • Author(s)
      Takami Taro
    • Organizer
      10th ISSCR Annual meeting
    • Place of Presentation
      バシフィコ横浜(横浜)
    • Related Report
      2012 Research-status Report
  • [Presentation] Basic studies for the development of a less invasive liver regeneration therapy using thermoreactive organic/inorganic nanocomposite gels-cultured bone marrow derived cells2012

    • Author(s)
      Takami Taro
    • Organizer
      10th ISSCR Annual meeting
    • Place of Presentation
      バシフィコ横浜(横浜)
    • Related Report
      2012 Research-status Report
  • [Remarks] ABMI(自己骨髄細胞投与)療法

    • URL

      http://www.ichinai-yamaguchi.jp/contents4/?categoryId=7

    • Related Report
      2014 Annual Research Report
  • [Remarks] ABMi(自己骨髄細胞投与)療法

    • URL

      http://www.ichinai-yamaguchi.jp/contents4/?categoryId=7

    • Related Report
      2012 Research-status Report
  • [Patent(Industrial Property Rights)] ソラフェニブの副作用低減剤2012

    • Inventor(s)
      山本 直樹   山崎 隆弘   坂井田 功
    • Industrial Property Rights Holder
      山口大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2012-11-05
    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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