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Development of new therapy with mesenchymal stem cell for reperfusion injury following reperfusion therapy

Research Project

Project/Area Number 16K10730
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurosurgery
Research InstitutionSapporo Medical University

Principal Investigator

Honmou Osamu  札幌医科大学, 医学部, 教授 (90285007)

Co-Investigator(Kenkyū-buntansha) 佐々木 祐典  札幌医科大学, 医学部, 講師 (20538136)
浪岡 愛  札幌医科大学, 医学部, 研究員 (60748995)
中崎 公仁  札幌医科大学, 医学部, 研究員 (70722461)
浪岡 隆洋  札幌医科大学, 医学部, 研究員 (70748996)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords脳梗塞 / 骨髄幹細胞 / 再灌流障害 / 骨髄間葉系幹細胞
Outline of Final Research Achievements

Reperfusion therapy with rtPA is the standard therapy for stroke. However, hemorrhagic complications can result. Intravenous infusion of MSCs provides therapeutic efficacy. One suggested mechanism is inhibition of endothelial dysfunction. Four groups were studied: 1) NS+vehicle, 2) rtPA+vehicle, 3) NS+MSCs, 4) rtPA+MSCs. The MSC-treated groups (3,4) experienced a greater reduction in the incidence rate of intracerebral hemorrhage and hemorrhagic volume after tMCAO even if rtPA was received. Behavioral testing indicated that MSC-infused groups had greater improvement, but rtPA+MSCs provided greater improvement than MSCs alone. The rCBF ratio of rtPA groups (2,4) was similar at 2 hours after reperfusion of tMCAO, but both were greater than that in non-rtPA groups. Infused MSCs may inhibit endothelial dysfunction to suppress hemorrhagic events and facilitate functional outcome. Combined therapy MSCs and rtPA facilitated early behavioral recovery.

Academic Significance and Societal Importance of the Research Achievements

虚血性脳血管障害に対する近年の血栓溶解療法や脳血管内治療の急速な進歩により、再灌流障害への対応は、急いで対応すべき課題となっている。本研究では、MSC治療により、血管内皮機能の破綻が抑制により出血性合併症を減少させ、運動機能の改善に貢献することを明らかにした。さらに、本研究では、MSC療法とリハビリテーションの併用、新しい治療メカニズムの解明のほかに、慢性期脳梗塞、脳幹梗塞、脳小血管病、低酸素性虚血性脳症に対するMSC療法の展開に関しても研究を行い、良好な結果を報告している。以上より、MSC治療の今後の臨床における有用性を考慮した際の社会的意義は高いものと考えられる。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (14 results)

All 2018 2017 2016 Other

All Int'l Joint Research (2 results) Journal Article (7 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 2 results,  Acknowledgement Compliant: 1 results) Presentation (4 results) (of which Int'l Joint Research: 1 results,  Invited: 4 results) Book (1 results)

  • [Int'l Joint Research] Yale University(米国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] Yale University School of Medicine(米国)

    • Related Report
      2016 Research-status Report
  • [Journal Article] Intravenous infusion of mesenchymal stem cells promotes functional recovery in a rat model of chronic cerebral infarction2018

    • Author(s)
      Namioka Takahiro、Namioka Ai、Sasaki Masanori、Kataoka-Sasaki Yuko、Oka Shinichi、Nakazaki Masahito、Onodera Rie、Suzuki Junpei、Sasaki Yuichi、Nagahama Hiroshi、Kocsis Jeffery D.、Honmou Osamu
    • Journal Title

      Journal of Neurosurgery

      Volume: Oct1 Issue: 4 Pages: 1-8

    • DOI

      10.3171/2018.5.jns18140

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Intravenous infusion of mesenchymal stem cells for protection against brainstem infarction in a persistent basilar artery occlusion model in the adult rat2018

    • Author(s)
      Namioka Ai、Namioka Takahiro、Sasaki Masanori、Kataoka-Sasaki Yuko、Oka Shinichi、Nakazaki Masahito、Onodera Rie、Suzuki Junpei、Sasaki Yuichi、Nagahama Hiroshi、Kocsis Jeffery D.、Honmou Osamu
    • Journal Title

      Journal of Neurosurgery

      Volume: Oct1 Issue: 4 Pages: 1-9

    • DOI

      10.3171/2018.4.jns173121

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Functional recovery after the systemic administration of mesenchymal stem cells in a rat model of neonatal hypoxia-ischemia2018

    • Author(s)
      Sakai Takuro、Sasaki Masanori、Kataoka-Sasaki Yuko、Oka Shinichi、Nakazaki Masahito、Fukumura Shinobu、Kobayashi Masaki、Tsutsumi Hiroyuki、Kocsis Jeffery D.、Honmou Osamu
    • Journal Title

      Journal of Neurosurgery: Pediatrics

      Volume: 22 Issue: 5 Pages: 513-522

    • DOI

      10.3171/2018.5.peds1845

    • Related Report
      2018 Annual Research Report
  • [Journal Article] 8. Evaluation of the Therapeutic Mechanisms in Regeneration Therapy for Cerebral Infarction Using Pre-clinical Magnetic Resonance Imaging2018

    • Author(s)
      Nagahama Hiroshi、Suzuki Junpei、Sasaki Masanori、Nakazaki Masahito、Honmou Osamu
    • Journal Title

      Japanese Journal of Radiological Technology

      Volume: 74 Issue: 7 Pages: 722-725

    • DOI

      10.6009/jjrt.2018_JSRT_74.7.722

    • NAID

      130007399800

    • ISSN
      0369-4305, 1881-4883
    • Related Report
      2018 Annual Research Report
  • [Journal Article] Preservation of interhemispheric cortical connections through corpus callosum following intravenous infusion of mesenchymal stem cells in a rat model of cerebral infarction2018

    • Author(s)
      Nagahama Hiroshi、Nakazaki Masahito、Sasaki Masanori、Kataoka-Sasaki Yuko、Namioka Takahiro、Namioka Ai、Oka Shinichi、Onodera Rie、Suzuki Junpei、Sasaki Yuichi、Kocsis Jeffery D.、Honmou Osamu
    • Journal Title

      Brain Research

      Volume: 1695 Pages: 37-44

    • DOI

      10.1016/j.brainres.2018.05.033

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Elevated brain derived neurotrophic factor (BDNF) levels in plasma but not serum reflect in vivo functional viability of infused mesenchymal stem cells after middle cerebral artery occlusion in rat.2017

    • Author(s)
      Nakamura H, Sasaki Y, Sasaki M, Kataoka-Sasaki Y, Oka S, Nakazaki M, Namioka T, Namioka A, Onodera R, Suzuki J, Nagahama H, Mikami T, Wanibuchi M, Kocsis JD, Honmou O.
    • Journal Title

      J Neurosurg Sci.

      Volume: 印刷中 Issue: 4 Pages: 926-926

    • DOI

      10.3171/2016.8.jns16240

    • Related Report
      2017 Research-status Report 2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Elevated brain derived neurotrophic factor (BDNF) levels in plasma but not serum reflect in vivo functional viability of infused mesenchymal stem cells after middle cerebral artery occlusion in rat.2017

    • Author(s)
      Nakamura H, Sasaki Y, Sasaki M, Kataoka-Sasaki Y, Oka S, Nakazaki M, Namioka T, Namioka A, Onodera R, Suzuki J, Nagahama H, Mikami T, Wanibuchi M, Kocsis JD, Honmou O.
    • Journal Title

      Journal of Neurosurgical Sciences

      Volume: Feb 8 Issue: 1

    • DOI

      10.23736/s0390-5616.17.03989-3

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] 脳卒中と細胞治療:臨床への諸問題2018

    • Author(s)
      本望修
    • Organizer
      STROKE 2018、福岡
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 脳梗塞と脊髄損傷の再生医療―医師主導治験による実用化―2017

    • Author(s)
      本望修
    • Organizer
      第23回 日本脳神経外科救急学会、奈良
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] Intravenous Transplantation of Autologous Mesenchymal Stem Cells Derived Bone Marrow into Stroke and Spinal Cord Injury Patients.2016

    • Author(s)
      Honmou O
    • Organizer
      日米先端医療技術事業化会議
    • Place of Presentation
      ゴールデンゲートクラブ、サンフランシスコ(USA)
    • Year and Date
      2016-11-22
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 脳梗塞に対する骨髄間葉系幹細胞移植2016

    • Author(s)
      本望修
    • Organizer
      第22回日本遺伝子細胞治療学会学術集会
    • Place of Presentation
      虎ノ門ヒルズフォーラム(東京都港区)
    • Year and Date
      2016-07-30
    • Related Report
      2016 Research-status Report
    • Invited
  • [Book] Cell Therapy Against Cerebral Stroke2017

    • Author(s)
      Sasaki M and Honmou O
    • Total Pages
      156
    • Publisher
      Springer
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2022-02-16  

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