Improvement in neural function following intravenous infusion of mesenchymal stem cells in experimental cerebral stroke

Research Project

Project/Area Number	17K10901
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	Suzuki Junpei 札幌医科大学, 医学部, 研究員 (00572596)
Co-Investigator(Kenkyū-buntansha)	佐々木祐典札幌医科大学, 医学部, 講師 (20538136) 長濱宏史札幌医科大学, 医学部, 研究員 (20725676) 中崎公仁札幌医科大学, 医学部, 研究員 (70722461) 本望修札幌医科大学, 医学部, 教授 (90285007)
Project Period (FY)	2017-04-01 – 2020-03-31
Project Status	Completed (Fiscal Year 2019)
Budget Amount *help	¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000) Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000) Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords	脳梗塞 / 神経可塑性 / 骨髄間葉系幹細胞 / 再生医学
Outline of Final Research Achievements	Intravenous of mesenchymal stem cells (MSCs) following cerebral infarction exerts functional recovery. Previous study has suggested potential therapeutic mechanisms that promote neuroprotection and synaptogenesis, secretion of neurotrophic factors, remodeling of neural circuits, and elevation of trophic factors. In addition to these mechanisms, we hypothesized that restored interhemispheric connectivity might be an additional mechanism of neural improvements. In this study, we have demonstrated that there was anatomical restoration of cortical interhemispheric connections after infused MSCs in middle cerebral artery occlusion (MCAO). These results suggest that distinct preservation of interhemispheric cortical connections through corpus callosum was preserved by intravenous infusion of MSCs. This anatomical preservation of the motor cortex in the contralateral hemisphere may contribute to improvements in neural function after MSC therapy for cerebral stroke.
Academic Significance and Societal Importance of the Research Achievements	実験的脳梗塞に対する骨髄間葉系幹細胞の経静脈的投与は，すでに臨床における安全性や有効性の検討がなされている．本研究における研究成果によって，骨髄間葉系幹細胞の経静脈的投与による治療効果を発揮するメカニズムとして，骨髄間葉系幹細胞の投与によって，脳梁を介する両側大脳皮質運動野の連絡線維の保護が惹起され，それが神経機能の回復に貢献している可能性を明らかにしたことは，骨髄間葉系幹細胞の経静脈的投与によって，病側脳のみならず反対側の皮質に対して喪失した神経機能の回復に貢献するメカニズムが作動することを示唆しており，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．