Mesenchymal stem cell therapy for experimental stroke

• Project/Area Number: 19K09461
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56010:Neurosurgery-related
• Research Institution: Sapporo 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, 准教授 (20538136) ; 小野寺 理恵 札幌医科大学, 医学部, 客員講師 (60393328) ; 岡 真一 札幌医科大学, その他部局等, 講師 (70789453) ; 佐々木 優子 札幌医科大学, 医学部, 助教 (80631142)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); 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); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 骨髄幹細胞 / 脳梗塞

Outline of Research at the Start

骨髄幹細胞によって誘導された神経回路の再構築が、どのようなメカニズムで起こっているのかを形態学的解析、機能分子解析、分子生物学的解析を駆使することで解明しようとの着想に至った。神経回路の再構築における分子メカニズムを解明することで、脳梗塞における神経の可塑性をさらに亢進させ、より高い再生能を発揮する、次世代型細胞医薬品の開発が可能となると考えている。

Outline of Final Research Achievements

In this study, we demonstrated that the therapeutic efficacy of intravenous infusion of mesenchymal stem cells (MSCs) was enhanced via induced neural plasticity in the whole brain using MRI diffusion tensor imaging. We also showed that repeated systemic administration of MSCs over 3 weeks resulted in greater functional improvement as compared to single administration and/or vehicle infusion. Administration of MSCs is associated with the promotion of whole interhemispheric connectivity through the corpus callosum even in the chronic phase of cerebral infarction.

Academic Significance and Societal Importance of the Research Achievements

本研究では、脳梗塞に対するMSC治療によって全脳における神経可塑性の亢進が惹起され、運動機能や高次脳機能の回復に貢献する可能性が高いことを示した。しかも、神経可塑性の亢進は急性期に限らず惹起されるという新たな結果も得られることができた。また、可塑性をさらに高めるために、間隔をあけた複数回投与で、治療効果の上乗せを得ることができた。このように本研究の結果は、適応疾患の拡大、効果のさらなる向上につなげることができると考えられ、MSC治療の今後の臨床における有用性を考慮した際における学術的・社会的意義は高いものと考えられる。

Research Products

• [Int'l Joint Research] Yale University(米国)
• [Int'l Joint Research] Yale University(米国)
• [Int'l Joint Research] Yale University(米国)
• [Journal Article] Repeated intravenous infusion of mesenchymal stem cells for enhanced functional recovery in a rat model of chronic cerebral ischemia (2021)
  • Author(s): Takemura Mitsuhiro、Sasaki Masanori、Kataoka-Sasaki Yuko、Kiyose Ryo、Nagahama Hiroshi、Oka Shinichi、Ukai Ryo、Yokoyama Takahiro、Kocsis Jeffery D.、Ueba Tetsuya、Honmou Osamu
  • Journal Title: Journal of Neurosurgery Volume: － Issue: 2 Pages: 1-10
  • DOI: 10.3171/2021.8.jns21687
  • Peer Reviewed
• [Journal Article] Intravenous Infusion of Mesenchymal Stem Cells Enhances Therapeutic Efficacy of Reperfusion Therapy in Cerebral Ischemia (2021)
  • Author(s): Kiyose Ryo、Sasaki Masanori、Kataoka-Sasaki Yuko、Nakazaki Masahito、Nagahama Hiroshi、Magota Hirotoshi、Oka Shinichi、Ukai Ryo、Takemura Mitsuhiro、Yokoyama Takahiro、Kocsis Jeffery D.、Honmou Osamu
  • Journal Title: World Neurosurgery Volume: 149 Pages: e160-e169
  • DOI: 10.1016/j.wneu.2021.02.056
• [Journal Article] Focal brainstem infarction in the adult rat (2021)
  • Author(s): Namioka Ai、Namioka Takahiro、Sasaki Masanori、Kocsis Jeffery D.、Honmou Osamu
  • Journal Title: Lab Animal Volume: 50 Issue: 4 Pages: 97-107
  • DOI: 10.1038/s41684-021-00722-1
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Diseases as the Target of Cellular Therapy with Mesenchymal Stem Cells. (2020)
  • Author(s): 1)Sasaki M, Oka S, Kataoka-Sasaki Y, Kocsis JD, Honmou O.
  • Journal Title: World Neurosurg. Volume: 135 Pages: 375-376
  • DOI: 10.1016/j.wneu.2019.12.137
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Intravenous infusion of mesenchymal stem cells improves impaired cognitive function in a cerebral small vessel disease model. Neuroscience. (2019)
  • Author(s): 3)Nakazaki M, Sasaki M, Kataoka-Sasaki Y, Oka S, Suzuki J, Sasaki Y, Nagahama H, Hashi K, Kocsis JD, Honmou O.
  • Journal Title: J Neuroscience. Volume: 408 Pages: 361-377
  • DOI: 10.1016/j.neuroscience.2019.04.018
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Prevention of neointimal hyperplasia induced by an endovascular stent via intravenous infusion of mesenchymal stem cells. (2019)
  • Author(s): 2)Nakazaki M, Oka S, Sasaki M, Kataoka-Sasaki Y, Onodera R, Komatsu K, Iihoshi S, Hiroura M, Kawaguchi A, Kocsis JD, Honmou O.
  • Journal Title: J Neurosurg. Volume: 4 Issue: 6 Pages: 1-13
  • DOI: 10.3171/2019.7.jns19575
  • Peer Reviewed / Open Access / Int'l Joint Research