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Development of Adipose derived meschymal stem cell therapy for liver cirrhosis

Research Project

Project/Area Number 25462096
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Digestive surgery
Research InstitutionKyushu University

Principal Investigator

Akahoshi Tomohiko  九州大学, 医学(系)研究科(研究院), 准教授 (20336019)

Co-Investigator(Kenkyū-buntansha) Hashizume Makoto  九州大学, 大学院医学研究院, 教授 (90198664)
Murata Masaharu  九州大学, 大学院医学研究院, 准教授 (30304744)
富川 盛雅  九州大学, 大学院医学研究院, 特任准教授 (60325454)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Keywords間葉系幹細胞 / 肝硬変 / 幹細胞治療 / 門脈圧亢進症 / 脂肪由来間葉系幹細胞 / 非代償肝硬変 / 肝増殖因子
Outline of Final Research Achievements

Background:Recent studies show that adipose tissue-derived mesenchymal stem cells(ADSC) have potential clinical applications. Here, we investigated the effect of adipose tissue-derived mesenchymal stem cells infusion on a liver fibrosis rat model and elucidated the underlying mechanism.Result:bFGF treatment markedly improved the proliferation, differentiation, and hepatocyte growth factor expression ability of ADSC. Although ADSC infusion alone slightly ameliorated liver functions and suppressed fibrosis progression, bFGF-treatment significantly enhanced the therapeutic effect in association with elevated hepatocyte growth factor expression. Co-culture with ADSC led to induction of hepatic stellate cell apoptosis and enhanced hepatocyte proliferation. Mechanism investigation revealed that co-culture with adipose tissue-derived mesenchymal stem cells activated c-jun N-terminal kinase-p53 signaling in hepatic stellate cell and promoted apoptosis.

Report

(3 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (19 results)

All 2015 2014 2013 2012

All Journal Article (8 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 8 results,  Acknowledgement Compliant: 1 results,  Open Access: 2 results) Presentation (9 results) (of which Invited: 1 results) Book (2 results)

  • [Journal Article] Basic FGF-treated adipose tissue-derived mesenchymel stem cell infusion ameliorate liver cirrhosis via paracrine HGF2015

    • Author(s)
      Tang W, Aakahoshi T, Piao J, Narahara S, Murata M, Kawano T, Hamano N, Ikeda T, Hashizume M
    • Journal Title

      Journal of Gastroenterology and Hepatology

      Volume: 20 Issue: 6 Pages: 1065-1074

    • DOI

      10.1111/jgh.12893

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Splenectomy enhances the therapeutic effect of adipose tissue-derived mesenchymal stem cell infusion on liver cirrhosis rats.2015

    • Author(s)
      Tang WP, Akahoshi T, Piao JS, Narahara S,Murata M, Kawano T, Hamano N, Ikeda T, Hashizume M
    • Journal Title

      Liver international.

      Volume: Online Issue: 8 Pages: 1151-1159

    • DOI

      10.1111/liv.12962

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comparison of recombinant human thrombomodulin and gabexate mesylate for treatment of disseminated intravascular coagulation (DIC) with sepsis following emergent gastrointestinal surgery: a retrospective study2015

    • Author(s)
      Akahoshi T, Sugimori H, Kaku N, Tokuda K, Nagata T, Noda E, Morita M, Hashizume M, Maehara Y
    • Journal Title

      Eur J Trauma Emerg Surg

      Volume: 41 Issue: 5 Pages: 531-8

    • DOI

      10.1007/s00068-014-0478-4

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Balloon-occluded retrograde transvenous obliteration is feasible for prolonged portosystemic shunts after living donor liver transplantation.2014

    • Author(s)
      Nagao Y, Akahoshi T, Uehara H, Hashimoto N, Kinjo N, Kawanaka H, Tomikawa M, Uchiyama H, Yoshizumi T, Soejima Y, Shirabe K, Maehara Y
    • Journal Title

      Surgery Today

      Volume: 44 Issue: 4 Pages: 633-639

    • DOI

      10.1007/s00595-013-0535-3

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] omparison of open, laparoscopic, and hand-assisted laparoscopic devascularization of the upper stomach and splenectomy for treatment of esophageal and gastric varices: a single-center experience.2014

    • Author(s)
      Akahoshi T, Uehara H, Tomikawa M, Kawanaka H, Hashizume M, Maehara Y.
    • Journal Title

      Asian J Endosc Surg.

      Volume: 7 Issue: 2 Pages: 138-144

    • DOI

      10.1111/ases.12096

    • Related Report
      2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Merits of prophylactic sclerotherapy for esophageal varices concomitant unresectable hepatocellular carcinoma : Prospective randomized study2013

    • Author(s)
      Akahoshi T, Tomikawa M, Tsutsumi N, Hashizume M, Maehara Y
    • Journal Title

      Dig Endosc

      Volume: 26 Issue: 2 Pages: 172-177

    • DOI

      10.1111/den.12119

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Characteristics of splenic CD8+ T cell exhaustion in patients with hepatitis C.2013

    • Author(s)
      Sumida K, Shimoda S, Iwasaka S, Hisamoto S, Kawanaka H, Akahoshi T, Ikegami T, Shirabe K, Shimono N, Maehara Y, Selmi C, Gershwin ME, Akashi K.
    • Journal Title

      Clin Exp Immunol

      Volume: 174 Issue: 1 Pages: 172-178

    • DOI

      10.1111/cei.12158

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Hepatic vein waveform and splenomegaly predict improvement of prothrombin time after splenectomy in hepatitis C virus-related cirrhotic patients.2012

    • Author(s)
      Kinjo N, Nagao Y, Akahoshi T, Masahiro K, Hashimoto N, Uehara H, Kawanaka H, Tomikawa M, Shirabe K, Hashizume M, Maehara Y.
    • Journal Title

      Hepatol Res.

      Volume: in press Issue: 9 Pages: 933-941

    • DOI

      10.1111/hepr.12040

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] 脾臓が門脈循環および肝機能に及ぼす影響についての検討.2015

    • Author(s)
      赤星朋比古、川中博文、橋爪 誠
    • Organizer
      第23回日本消化器関連学会週間(JDDW)
    • Place of Presentation
      東京
    • Year and Date
      2015-10-08
    • Related Report
      2015 Annual Research Report
  • [Presentation] 肝性脳症に対するB-RTOの治療成績.2015

    • Author(s)
      赤星朋比古、吉田佳弘、川中博文、富川盛雅、前原喜彦、橋爪 誠
    • Organizer
      第22回日本門脈圧亢進症学会総会
    • Place of Presentation
      神奈川
    • Year and Date
      2015-09-10
    • Related Report
      2015 Annual Research Report
  • [Presentation] 病的肥満症に対する減量手術のメタボリックサージェリーとしての効果.2015

    • Author(s)
      赤星朋比古、池田哲夫、宗崎良太、富川盛雅、橋爪 誠、前原喜彦
    • Organizer
      第70回日本消化器外科学会総会
    • Place of Presentation
      静岡
    • Year and Date
      2015-07-15
    • Related Report
      2015 Annual Research Report
  • [Presentation] 門脈大循環シャントによる肝性脳症に対するBalloon retrograde transvenous obliteration (B-RTO)の治療成績.2015

    • Author(s)
      赤星朋比古、池田哲夫、川中博文、橋爪 誠、前原喜彦
    • Organizer
      第51回日本肝臓学会総会
    • Place of Presentation
      熊本
    • Year and Date
      2015-05-21
    • Related Report
      2015 Annual Research Report
  • [Presentation] 病的肥満症に対する腹空鏡下スリーブ状胃切除術の治療の工夫と治療成績.2015

    • Author(s)
      赤星朋比古、池田哲夫、宗崎良太、堤 亮介、前原喜彦、橋爪 誠
    • Organizer
      第115回日本外科学会定期学術集会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-04-16
    • Related Report
      2015 Annual Research Report
  • [Presentation] MDCTによる下部食道の血行動態の把握とEVL後再発との関係2013

    • Author(s)
      赤星朋比古、家守雄大、川中博文、橋爪 誠、前原喜彦
    • Organizer
      日本門脈圧亢進症学会
    • Place of Presentation
      名古屋
    • Related Report
      2013 Research-status Report
  • [Presentation] 脾摘が門脈循環に及ぼす影響2013

    • Author(s)
      赤星朋比古、川中博文、橋爪 誠、前原喜彦
    • Organizer
      日本臨床生理学会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] 脾摘が門脈循環に及ぼす影響2013

    • Author(s)
      赤星朋比古、川中博文、池田哲夫、橋爪 誠
    • Organizer
      日本内視鏡外科学会総会
    • Place of Presentation
      福岡
    • Related Report
      2013 Research-status Report
  • [Presentation] 食道胃静脈瘤における新しい治療戦略―抗ウイルス療法と腹腔鏡下脾臓摘出術の意義 について2013

    • Author(s)
      赤星朋比古、富川盛雅、神代竜一、戸島剛男、調 憲、橋爪 誠、前原喜彦
    • Organizer
      日本外科学会
    • Place of Presentation
      福岡
    • Related Report
      2013 Research-status Report
  • [Book] Atlas of Laparoscopic Hepato-Pancreato-Biliary Surgery.2015

    • Author(s)
      Hashizume M, Tomikawa M, Akahoshi T
    • Total Pages
      591
    • Publisher
      Cine-Med
    • Related Report
      2015 Annual Research Report
  • [Book] 最新 肝胆膵脾手術アトラス IV脾臓5 門脈亢進症に対するシャント手術2013

    • Author(s)
      赤星朋比古、橋爪 誠:
    • Total Pages
      9
    • Publisher
      金原出版
    • Related Report
      2013 Research-status Report

URL: 

Published: 2014-07-25   Modified: 2019-07-29  

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