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Therapeutic potential of mesenchymal stem cells for treatment of aortic aneurysm

Research Project

Project/Area Number 26713043
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypePartial Multi-year Fund
Research Field Cardiovascular surgery
Research InstitutionNagoya University

Principal Investigator

Ogata Aika  名古屋大学, 医学系研究科, 特任助教 (70718311)

Project Period (FY) 2014-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥23,920,000 (Direct Cost: ¥18,400,000、Indirect Cost: ¥5,520,000)
Fiscal Year 2017: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2016: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2015: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2014: ¥13,910,000 (Direct Cost: ¥10,700,000、Indirect Cost: ¥3,210,000)
Keywords大動脈瘤 / 間葉系幹細胞 / シグナル伝達 / エクソソーム / 抗炎症作用 / microRNA / 超音波診断装置 / miRNA / 幹細胞療法 / 細胞治療 / 静脈内投与 / 治癒メカニズム / 細胞療法 / エラスチン
Outline of Final Research Achievements

An aortic aneurysm (AA) develops as a result of atherosclerosis and chronic inflammation. Surgical repair of AA is effective treatment to prevent rupture. However, the surgical procedures for thoracic and thoracoabdominal AA are extremely invasive and associated with high mortality and morbidity. We have reported that intravenous injection of mesenchymal stem cells (MSCs) could reduce the morbidity rate of aortic aneurysm by anti-inflammatory and tissue repair properties of MSCs. In this study, echographic measurements showed that the maximum aortic diameters of MSC-treated mice were significantly shorter than saline injection throughout 1 week after injection. In addition we demonstrated that the therapeutic mechanism of MSC-mediated AA regression contributed to regulation of the NF-kB, STAT, Smad3 and Akt signaling pathways, MSC-derived exosomes, and microRNAs secreted from MSC.

Academic Significance and Societal Importance of the Research Achievements

高齢者・メタボリック症候群人口の増加を背景に、大動脈瘤罹患患者数は年々増加している。65歳以上の6-9%に腹部大動脈瘤が形成されているとの報告がある。標準的な治療法は人工血管置換術で、瘤破裂の予防効果は絶大だが、特に上行・弓部や胸腹部大動脈の人工血管置換術は、非常に手術侵襲が大きく、手術死亡率・合併症発症率も高い。従って、大動脈瘤治療の低侵襲化は国民的課題である。本研究では、成人の骨髄などに存在する間葉系幹細胞を利用し、静脈内投与することにより、抗炎症作用等を介した大動脈瘤径の拡大抑制効果が得られたことを明らかにした。この成果は、大動脈瘤に対する間葉系幹細胞治療の可能性を示した。

Report

(5 results)
  • 2018 Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • Research Products

    (6 results)

All 2017 2015

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (5 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Bone marrow-derived mesenchymal stromal cells regress aortic aneurysm via the NF-kB, Smad3 and Akt signaling pathways.2017

    • Author(s)
      Yamawaki-Ogata A, Oshima H, Usui A, Narita Y.
    • Journal Title

      Cytotherapy

      Volume: 19 Issue: 10 Pages: 1167-1175

    • DOI

      10.1016/j.jcyt.2017.07.010

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 幹細胞による大動脈瘤治療における作用機序と新たな治療戦略への展望2017

    • Author(s)
      緒方藍歌、成田裕司、碓氷章彦
    • Organizer
      第16回再生心臓血管外科治療研究会
    • Place of Presentation
      グランドニッコー東京台場(東京都港区)
    • Year and Date
      2017-02-27
    • Related Report
      2016 Annual Research Report
  • [Presentation] 間葉系幹細胞を用いた大動脈瘤治療における分子メカニズムの解明2015

    • Author(s)
      緒方藍歌、大島英揮、碓氷章彦、成田裕司
    • Organizer
      第36回日本炎症・再生医学会
    • Place of Presentation
      虎ノ門ヒルズフォーラム(東京都港区)
    • Year and Date
      2015-07-21 – 2015-07-22
    • Related Report
      2014 Annual Research Report
  • [Presentation] 間葉系幹細胞を用いた大動脈瘤治療における分子メカニズムの解明2015

    • Author(s)
      緒方藍歌、大島英揮、碓氷章彦、成田裕司
    • Organizer
      第36回日本炎症・再生医学会
    • Place of Presentation
      虎ノ門ヒルズフォーラム(東京都港区)
    • Year and Date
      2015-07-21
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Bone Marrow-derived Mesenchymal Stem Cells treated aortic aneurysm via NF-KB and AKT signal pathway in mice2015

    • Author(s)
      Aika Yamawaki-Ogata, Akihiko Usui, Yuji Narita
    • Organizer
      International Society for Stem Cell Research 13th Annual meeting
    • Place of Presentation
      Stockholm, Sweden
    • Year and Date
      2015-06-24
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 大動脈瘤に対する細胞治療におけるシグナル伝達機構2015

    • Author(s)
      緒方藍歌、成田裕司、佐藤恵一、大島英揮、碓氷章彦
    • 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

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Published: 2014-04-04   Modified: 2020-03-30  

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