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Establishment of treatment method using activated MSC for autoimmune myocarditis

Research Project

Project/Area Number 19K08568
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53020:Cardiology-related
Research InstitutionOsaka Habikino Medical Center (2020-2021)
Fujita Health University (2019)

Principal Investigator

Okura hanayuki  地方独立行政法人大阪府立病院機構大阪はびきの医療センター(臨床研究センター), 次世代創薬創生センター, 研究員(移行) (20589684)

Co-Investigator(Kenkyū-buntansha) 松山 晃文  地方独立行政法人大阪府立病院機構大阪はびきの医療センター(臨床研究センター), 次世代創薬創生センター, センター長 (10423170)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords自己免疫性心筋炎 / 抗炎症 / 毛細血管再構築 / 末梢神経再生 / 間葉系幹細胞 / 心筋炎
Outline of Research at the Start

自己免疫性心筋炎の治療targetが抗炎症、毛細血管網・静脈系・リンパ管、末梢神経支配の再生であると仮説をたて、活性化MSCが分泌するsecretomeがそれら治療targetに作用するとの新規戦略が、自己免疫性心筋炎治療法開発に妥当であるか検討する。これまで、160種の生理活性物質にて培養したMSCのDNA micro Arrayから、特にIL-1βが、治療targetである抗炎症、毛細血管構築、静脈・リンパ管構築の作用をもつsecretomeを産生することを見出し、IL-1βをMSCの活性化に選択した。IL-1β活性化MSCが自己免疫性心筋炎モデルに有効であることを示し、なぜ効果があったのかどの治療targetにて効果を示したのかを理解する。

Outline of Final Research Achievements

Therapeutic strategies for autoimmune myocarditis are anti-inflammatory in the acute phase and myocardial tissue regeneration in the chronic phase. Regarding the anti-inflammatory effect, priming of MSC increased PGE2 synthase and G-CSF about 10 times or more about 1000 times or more, respectively. Arterial and blood vessels, and peripheral nerve were examined by markers in the specimens. The primed MSC administration augmented the number of positive arterial and venous vessels, and NF68 than those of naive MSC administration, indicating that primed MSC repairs and regenerates arteries and veins and peripheral nerve innervation that are essential for repairing chronically injured tissue. These results hinted us that the primed MSC could improve the prognosis of autoimmune myocarditis.

Academic Significance and Societal Importance of the Research Achievements

活性化MSCは自己免疫性心筋炎への新規治療法となり、急性期の抗炎症、慢性期の血流回復、遠隔期の神経支配回復による予後改善に寄与すると想定される。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (4 results)

All 2019

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (3 results)

  • [Journal Article] Trends in clinical trials for stroke by cell therapy: data mining ClinicalTrials.gov and the ICTRP portal site.2019

    • Author(s)
      Takaharu Negoro, Hanayuki Okura, Midori Maehata, Shigekazu Hayashi, Satoru Yoshida, Nozomi Takada, Akifumi Matsuyama.
    • Journal Title

      npj Regenerative Medicine.

      Volume: 4,20 Issue: 1 Pages: 1-6

    • DOI

      10.1038/s41536-019-0082-7

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Anti-Solid Tumor CAR-T Platform2019

    • Author(s)
      松山晃文・大倉華雪
    • Organizer
      再生医療Japan2019
    • Related Report
      2019 Research-status Report
  • [Presentation] Genetic instability should be checked inclinical application for pluripotent stem cell-derived clinical products?2019

    • Author(s)
      松山晃文・大倉華雪・吉田悟・高田のぞみ・林重一
    • Organizer
      第57回日本臓器学会大会
    • Related Report
      2019 Research-status Report
  • [Presentation] Current technical status of the detection methods of potetial mass formation caused by impurities of PSCs-direved products.2019

    • Author(s)
      松山晃文・大倉華雪・吉田悟・高田のぞみ・林重一
    • Organizer
      第57回日本臓器学会大会
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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