2019 Fiscal Year Final Research Report

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

Research Project

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Project/Area Number	17K10902
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Neurosurgery
Research Institution	Sapporo 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
Keywords	脊髄損傷 / 骨髄幹細胞 / 移植 / 再生医療 / 神経可塑性
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.
Free Research Field	整形外科学
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。