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Elucidation of the molecular cytological mechanism by which mesenchymal stem cell-derived exosomes promote tendon repair

Research Project

Project/Area Number 20K22740
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeMulti-year Fund
Review Section 0802:Biomedical structure and function and related fields
Research InstitutionHiroshima University

Principal Investigator

Hayashi Yuta  広島大学, 医系科学研究科(医), 寄附講座助教 (20881296)

Project Period (FY) 2020-09-11 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords間葉系幹細胞 / 細胞外小胞 / 腱修復 / 細胞老化 / 糖鎖 / エクソソーム / Scleraxis / スクレラキシス
Outline of Research at the Start

先行研究において運動器細胞に分化することができる間葉系幹細胞(MSC)から分泌されるエクソソームを投与すると、マウスアキレス腱修復が促進されることを実証した。本研究ではその分子細胞学機序を解明する。また、同研究でエクソソーム表面に発現してる糖鎖発現パターンによりエクソソームの質が評価できることが示唆された。本研究ではその糖鎖がエクソソームのどのような機能に関与しているかを明らかにする。

Outline of Final Research Achievements

It was clarified that extracellular vesicles derived from normal mesenchymal stem cells have the ability to promote proliferation and migration to tendon fibroblasts, and verification using model mice also revealed that they promote Achilles tendon repair. rice field. On the other hand, extracellular vesicles derived from senescence mesenchymal stem cells had lower ability to promote repair than those derived from normal cells. Therefore, when the glycans on the surface of the vesicles were evaluated using a lectin array, TJA-II, which is a fucose-specific glycans, was significantly highly expressed in extracellular vesicles derived from normal cells. In other words, it was suggested that the quality of extracellular vesicles could be evaluated using surface glycans.

Academic Significance and Societal Importance of the Research Achievements

細胞外小胞の臨床応用へ向けての大きな課題が、細胞外小胞の組織修復促進能(いわゆる質)を評価する方法と、高い質を持つ細胞外小胞を単離する方法である。本研究では小胞表面の糖鎖を評価することで小胞の質を評価できる可能性を示唆した。本法は内容物ではなく小胞表面の糖鎖を測定することで質を直接評価きる点に優位性がある。さらに糖鎖を利用したカラムなどを開発することで、効率的に高品質な細胞外小胞のみを単離できる方法を確立でき、細胞外小胞の臨床応用に向けて貢献できる可能性がある。

Report

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

    (1 results)

All 2022

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

  • [Journal Article] The therapeutic capacity of bone marrow MSC-derived extracellular vesicles in Achilles tendon healing is passage-dependent and indicated by specific glycans.2022

    • Author(s)
      Hayashi Y, Yimiti D, Sanada Y, Ding C, Omoto T, Ogura T, Nakasa T, Ishikawa M, Hiemori K, Tateno H, Miyaki S, Adachi N.
    • Journal Title

      FEBS Lett.

      Volume: 596(8) Issue: 8 Pages: 1047-1058

    • DOI

      10.1002/1873-3468.14333

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access

URL: 

Published: 2020-09-29   Modified: 2023-01-30  

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