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Gene therapy and application of iPS cells to major organ regeneration in septic multiple organ failure

Research Project

Project/Area Number 25293365
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Emergency medicine
Research InstitutionNagoya University

Principal Investigator

Matsuda Naoyuki  名古屋大学, 医学(系)研究科(研究院), 教授 (50332466)

Project Period (FY) 2013-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000)
Fiscal Year 2015: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2014: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2013: ¥11,440,000 (Direct Cost: ¥8,800,000、Indirect Cost: ¥2,640,000)
Keywords敗血症 / 多臓器不全 / 線維芽細胞 / 転写因子 / 肺線維症 / Oct3/4 / Sox2 / Klf4 / c-Myc / 線維症 / 遺伝子治療 / 播種性血管内凝固症候群 / 再生治療 / iPS細胞 / 肺線維化
Outline of Final Research Achievements

Sepsis causes fibroblast proliferation in various organs following systemic inflammation due to infection. For this process, we studied growth control of fibroblasts in mouse sepsis model and human fibroblast cell culture system. Male BALB-C mice of 8 to 12 weeks as a sepsis animal model were used to evaluate pathology by cecal ligation and puncture (CLP). Analysis of the distribution of fibroblasts using S100 calcium-binding protein, etc. showed an increase in fibroblasts in the lungs and the atrial fascia interface in the time course after CLP. In the study of cell culture of human fibroblast IMR-90, it was possible to evaluate that the β receptor activation by catecholamine and thrombin activity in systemic inflammation are strongly involved in fibroblast proliferation. It was revealed that fibroblast proliferation and organization was observed in association with inflammation of sepsis in the lung and heart.

Report

(5 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (15 results)

All 2017 2016 2015 2014

All Journal Article (8 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 8 results,  Acknowledgement Compliant: 3 results,  Open Access: 5 results) Presentation (7 results) (of which Invited: 1 results)

  • [Journal Article] Recent advances in the pathophysiology and molecular basis of sepsis-associated organ dysfunction: Novel therapeutic implications and challenges.2017

    • Author(s)
      Hattori Y, Hattori K, Suzuki T, Matsuda N.
    • Journal Title

      Pharmacol Ther

      Volume: S0163-7258(17) Pages: 30064-30065

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Regulation of the Cardiovascular System by Histamine.2017

    • Author(s)
      Hattori Y, Hattori K, Matsuda N.
    • Journal Title

      Handb Exp Pharmaco

      Volume: 241 Pages: 239-258

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Critical role of endogenous histamine in promoting end-organ tissue injury in sepsis.2016

    • Author(s)
      Hattori M, Yamazaki M, Ohashi W, Tanaka S, Hattori K, Todoroki K, Fujimori T, Ohtsu H, Matsuda N, Hattori Y.
    • Journal Title

      Intensive Care Med Exp

      Volume: 4(1) Pages: 36-36

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Alert cell strategy in SIRS-induced vasculitis: sepsis and endothelial cells.2016

    • Author(s)
      Naoyuki Matsuda
    • Journal Title

      J Intensive Care

      Volume: 4 Issue: 1 Pages: 21-21

    • DOI

      10.1186/s40560-016-0147-2

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Anti-Inflammatory Profile of Levosimendan in Cecal Ligation-Induced Septic Mice and in Lipopolysaccharide-Stimulated Macrophages.2015

    • Author(s)
      Qiang Wang, Hiroki Yokoo, Michinori Takashina, Kimimasa Sakata, Wakana Ohashi, Lobna A Abdelzaher, Takahiro Imaizumi, Takuya Sakamoto, Kohshi Hattori, Naoyuki Matsuda, Yuichi Hattori
    • Journal Title

      Critical Care Medicine

      Volume: 43巻,11号 Issue: 11 Pages: e508-e520

    • DOI

      10.1097/ccm.0000000000001269

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Inflammation-induced endothelial cell-derived extracellukar vesicles modulate the cellular status of pericytes.2015

    • Author(s)
      Yamamoto S., Niida S., Azuma E., Yanagibashi T., Muramatsu M., Huang TT., Sagara H., Higaki S., Ikutani M., Nagai Y., Takatsu K., Miyazaki K., Hamashima T., Mori H., Matsuda N., Ishii Y., Sasahara M.
    • Journal Title

      Scientific Reports

      Volume: 5 Issue: 1 Pages: 8505-8505

    • DOI

      10.1038/srep08505

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Alert cell strategy: mechanisms of inflammatory response and organ protection.2014

    • Author(s)
      Hatakeyama N, Matsuda N
    • Journal Title

      Curr Pharm Des

      Volume: 20 Pages: 5766-78

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The Japanese guidelines for the management of sepsis.2014

    • Author(s)
      Oda S, Aibiki M, Ikeda T, Imaizumi H, Endo S, Ochiai R, Kotani J, Shime N, Nishida O, Noguchi T, Matsuda N, Hirasawa H; Sepsis Registry Committee of The Japanese Society of Intensive Care Medicine.
    • Journal Title

      J Intensive Care

      Volume: 28 Issue: 1 Pages: 55-55

    • DOI

      10.1186/s40560-014-0055-2

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 救急診療を支える基礎基盤研究システム2016

    • Author(s)
      松田直之
    • Organizer
      第44回日本救急医学会学術集会・総会
    • Place of Presentation
      グランドプリンスホテル新高輪(東京都品川区)
    • Year and Date
      2016-11-17
    • Related Report
      2016 Annual Research Report
  • [Presentation] 線維芽細胞に対するドブタミンの増殖性作用の解析2016

    • Author(s)
      松田直之
    • Organizer
      第44回日本救急医学会学術集会・総会
    • Place of Presentation
      グランドプリンスホテル新高輪(東京都品川区)
    • Year and Date
      2016-11-17
    • Related Report
      2016 Annual Research Report
  • [Presentation] 線維芽細胞に対するトロンビンとAP-12016

    • Author(s)
      松田直之
    • Organizer
      第44回日本救急医学会学術集会・総会
    • Place of Presentation
      グランドプリンスホテル新高輪(東京都品川区)
    • Year and Date
      2016-11-17
    • Related Report
      2016 Annual Research Report
  • [Presentation] 繊維芽細胞に対するドブタミンの増殖性作用の解析2015

    • Author(s)
      山本尚範,松田直之,久保寺 敏,吉田拓也,東 倫子,江嶋正志,沼口 敦
    • Organizer
      第43回日本救急医学会学術集会
    • Place of Presentation
      東京国際フォーラム(東京都千代田区)
    • Year and Date
      2015-10-21
    • Related Report
      2015 Annual Research Report
  • [Presentation] 繊維芽細胞に対するトロンビンとAP-1活性の作用2015

    • Author(s)
      山本尚範,松田直之,久保寺 敏,吉田拓也,東 倫子,江嶋正志,沼口 敦
    • Organizer
      第43回日本救急医学会学術集会
    • Place of Presentation
      東京国際フォーラム(東京都千代田区)
    • Year and Date
      2015-10-21
    • Related Report
      2015 Annual Research Report
  • [Presentation] 肺線維症の病態と治療2014

    • Author(s)
      松田直之
    • Organizer
      第41回日本集中治療医学会学術集会・総会
    • Place of Presentation
      京都国際会議場( 京都)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Gene Therapy in Severe Sepsis with Acute Lung Injury2014

    • Author(s)
      Naoyuki Matsuda
    • Organizer
      Global Technology Community Conference Cell & Gene Therapy
    • Place of Presentation
      San Diego( 米国)
    • Related Report
      2013 Annual Research Report

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Published: 2013-05-21   Modified: 2019-07-29  

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