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Novel treatment using microglia preconditioned by oxygen glucose deprivation against cerebral hemorrhage

Research Project

Project/Area Number 18K07496
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52020:Neurology-related
Research InstitutionGifu University

Principal Investigator

SHIMOHATA TAKAYOSHI  岐阜大学, 大学院医学系研究科, 教授 (60361911)

Co-Investigator(Kenkyū-buntansha) 金澤 雅人  新潟大学, 脳研究所, 准教授 (80645101)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords低酸素低糖刺激 / ミクログリア / 末梢血単核球 / 脳出血 / 低酸素・低糖刺激
Outline of Final Research Achievements

In this study, we examined the changes in the properties of peripheral blood mononuclear cells (PBMCs), a precursor of microglia, by stimulating them with OGD, and found that OGD-PBMCs secrete vascular remodeling factors such as vascular endothelial growth factor (VEGF) and TGF-β. On the other hand, when OGD-PBMCs were administered transarterially on day 7 of ischemia in an animal model, they were found in the brain parenchyma and improved prognosis on day 28. Furthermore, we found that OGD-PBMCs can induce SSEA3-positive cells. In addition, OGD-PBMCs promoted migration through the blood-brain barrier. Furthermore, OGD-PBMCs promoted angiogenesis and neuronal axon extension. Finally, we developed an OGD device for clinical trials.

Academic Significance and Societal Importance of the Research Achievements

脳梗塞に対する細胞療法の検討がされている.骨髄間葉系幹細胞を用いた細胞療法は有望であるが,その普及を妨げる欠点として,1.得られる細胞数が少なく,専用の細胞プロセッシングセンター(CPC)で培養に2週間以上が必要であり,ごく一部の専門病院でしか行うことができないこと,2.iPS細胞を含む癌化の危険性(Kawai, JCBFM2010),3.きわめて高額であることがあげられる.本研究によるOGD-PBMCを用いた新しい細胞療法はこれらの欠点を克服し,一般病院でも安価に細胞療法が行われる治療法になる可能性があり,社会への貢献は大きいと考えている.

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (9 results)

All 2021 2020 2019 Other

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

  • [Journal Article] 総説 脳梗塞に対する低酸素低糖刺激末梢血単核球療法2020

    • Author(s)
      畠山公大,二宮至,小野寺理,下畑享良,金澤雅人
    • Journal Title

      BRAIN and NERVE

      Volume: 72 Issue: 10 Pages: 1097-1103

    • DOI

      10.11477/mf.1416201655

    • ISSN
      1344-8129, 1881-6096
    • Year and Date
      2020-10-01
    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cell Therapies under Clinical Trials and Polarized Cell Therapies in Pre-Clinical Studies to Treat Ischemic Stroke and Neurological Diseases: A Literature Review.2020

    • Author(s)
      Hatakeyama M, Ninomiya I, Otsu Y, Omae K, Kimura Y, Onodera O, Fukushima M, Shimohata T, Kanazawa M.
    • Journal Title

      Int J Mol Sci.

      Volume: 21 Issue: 17 Pages: 6194-6194

    • DOI

      10.3390/ijms21176194

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Strategies to prevent hemorrhagic transformation after reperfusion therapies for acute ischemic stroke: A literature review.2020

    • Author(s)
      Otsu Y, Namekawa M, Toriyabe M, Ninomiya I, Hatakeyama M, Uemura M, Onodera O, Shimohata T, Kanazawa M.
    • Journal Title

      J Neurol Sci.

      Volume: 419 Pages: 117217-117217

    • DOI

      10.1016/j.jns.2020.117217

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A novel therapeutic approach using peripheral blood mononuclear cells preconditioned by oxygen-glucose deprivation.2019

    • Author(s)
      Hatakeyama M, Kanazawa M, Ninomiya I, Omae K, Kimura Y, Takahashi T, Onodera O, Fukushima M, Shimohata T.
    • Journal Title

      Sci Rep.

      Volume: 9 Issue: 1 Pages: 16819-16819

    • DOI

      10.1038/s41598-019-53418-5

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Angiogenesis in the ischemic core: A potential treatment target?2019

    • Author(s)
      Kanazawa M, Takahashi T, Ishikawa M, Onodera O, Shimohata T, Del Zoppo GJ.
    • Journal Title

      J Cereb Blood Flow Metab.

      Volume: Mar 6 Issue: 5 Pages: 753-769

    • DOI

      10.1177/0271678x19834158

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] 脳梗塞に対する低酸素低糖刺激末梢血単核球を用いた細胞療法2020

    • Author(s)
      畠山公大,金澤雅人,二宮格,尾前薫,木村泰子,高橋哲哉,小野寺理,福島雅典,下畑享良
    • Organizer
      第63回日本脳循環代謝学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] トランスレーショナルリサーチの実践2019

    • Author(s)
      下畑 享良
    • Organizer
      第44回日本脳卒中学会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Book] 脳卒中エキスパート 神経保護・神経再生療法2021

    • Author(s)
      下畑 享良
    • Total Pages
      210
    • Publisher
      中外医学社
    • ISBN
      9784498328662
    • Related Report
      2020 Annual Research Report
  • [Remarks] 脳梗塞に対する治療薬開発を目指したトランスレーショナル・リサーチ

    • URL

      http://www.med.gifu-u.ac.jp/neurology/research/tr.html

    • Related Report
      2020 Annual Research Report 2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-12-28  

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