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Functional recovery following intravenous infusion of mesenchymal stem cells via induction of neural plasticity in chronic spinal cord injury

Research Project

Project/Area Number 17K10902
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

Morita Tomonori  札幌医科大学, 医学部, 研究員 (60723343)

Co-Investigator(Kenkyū-buntansha) 佐々木 祐典  札幌医科大学, 医学部, 講師 (20538136)
押切 勉  札幌医科大学, 医学部, 助教 (70754612)
廣田 亮介  札幌医科大学, 医学部, 研究員 (10815434)
中崎 公仁  札幌医科大学, 医学部, 研究員 (70722461)
鰐渕 昌彦  札幌医科大学, 医学部, 准教授 (30343388)
本望 修  札幌医科大学, 医学部, 教授 (90285007)
山下 敏彦  札幌医科大学, 医学部, 教授 (70244366)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords脊髄損傷 / 骨髄幹細胞 / 移植 / 再生医療 / 神経可塑性 / 骨髄間葉系幹細胞 / 慢性期
Outline of Final Research Achievements

Intravenous infusion of mesenchymal stem cells (MSCs) has been shown to provide functional improvements in spinal cord injury (SCI) through local therapeutic mechanisms that provide neuroprotection, remyelination, and axonal sprouting. Recent evidence has demonstrated that remote responses in the brain, as well as local responses in the injured spinal cord, can be induced after SCI. In the present study, we examined the brain response that might be associated with the functional improvements induced by the infused MSCs after SCI. Genome-wide RNA profiling was performed in the motor cortex of SCI rats at 3 days post-MSC or vehicle infusion. Then, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) data revealed that the seven behaviorally-associated differentially expressed genes (DEGs) had significant correlations with the behavioral function. These behaviorally-associated DEGs may be related to the functional recovery after systemic infusion of MSCs in SCI.

Academic Significance and Societal Importance of the Research Achievements

骨髄間葉系幹細胞(MSC)は経静脈的な全身投与により、神経保護作用や血管新生作用、損傷軸索の再生といった脊髄局所に限局した作用のみでなく、脳に対しても遺伝子発現の変化を移植後早期に促進することで、損傷上位のplasticityの賦活化を惹起し、機能回復に大きく関与していると考えられた。今後、MSCの協奏的に作用する多彩な治療メカニズムを解明していくことで、治療方法の乏しい脊髄損傷に対する作用効果がさらに優れた新たな治療法の開発や、未だ明確な治療法が確立していない他の難病への適応拡大にも繋がることが期待できると考える。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (5 results)

All 2019 Other

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

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

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Intravenous Infusion of Mesenchymal Stem Cells Alters Motor Cortex Gene Expression in a Rat Model of Acute Spinal Cord Injury2019

    • Author(s)
      Oshigiri Tsutomu、Sasaki Toru、Sasaki Masanori、Kataoka-Sasaki Yuko、Nakazaki Masahito、Oka Shinichi、Morita Tomonori、Hirota Ryosuke、Yoshimoto Mitsunori、Yamashita Toshihiko、Hashimoto-Torii Kazue、Honmou Osamu
    • Journal Title

      Journal of Neurotrauma

      Volume: 36 Issue: 3 Pages: 411-420

    • DOI

      10.1089/neu.2018.5793

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] 脊髄損傷患者に対する自家骨髄間葉系幹細胞移植療法2019

    • Author(s)
      森田智慶, 本望修, 山下敏彦
    • Journal Title

      医学のあゆみ

      Volume: 27 Pages: 647-650

    • Related Report
      2019 Annual Research Report
  • [Presentation] 急性期実験的脊髄損傷に対する骨髄間葉系幹細胞の経静脈的移植後の大脳皮質運動野の遺伝子発現変化の検討2019

    • Author(s)
      押切勉, 佐々木祐典, 廣田亮介, 森田智慶, 吉本三徳, 本望修, 山下敏彦
    • Organizer
      第48回日本脊椎脊髄病学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 急性期実験的脊髄損傷に対する骨髄間葉系幹細胞の経静脈的移植後の大脳皮質運動野の遺伝子発現変化の検討2019

    • Author(s)
      押切勉, 佐々木祐典, 廣田亮介, 森田智慶, 吉本三徳, 本望修, 山下敏彦
    • Organizer
      第92回日本整形外科学会学術総会
    • Related Report
      2019 Annual Research Report

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Published: 2017-04-28   Modified: 2021-02-19  

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