2021 Fiscal Year Final Research Report

Novel treatment for intracranial hemorrhage using amnion derived mesenchymal stem cells

Research Project

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Project/Area Number	19K09539
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	Hyogo Medical University
Principal Investigator	Yoshimura Shinichi 兵庫医科大学, 医学部, 教授 (40240353)
Co-Investigator(Kenkyū-buntansha)	高木俊範兵庫医科大学, 医学部, 講師 (00452152) 内田和孝兵庫医科大学, 医学部, 准教授 (10570674) 白川学兵庫医科大学, 医学部, 准教授 (50425112) 山原研一兵庫医科大学, 医学部, 准教授 (50450888) 中込隆之兵庫医科大学, 医学部, 教授 (80434950) 藏本要二兵庫医科大学, 医学部, 講師 (10604275)
Project Period (FY)	2019-04-01 – 2022-03-31
Keywords	脳出血 / 羊膜由来間葉系幹細胞 / 細胞治療
Outline of Final Research Achievements	Amnion-derived mesenchymal stem cells(MSCs) were administered intravenously in a mouse model of cerebral hemorrhage, with the earlier administration of more MSCs improving neurological function at two different volumes and times. The results also showed that MSCs with one-tenth the number of cells of adipose-derived MSCs, which were developed earlier, were equally or more effective. Tumor necrosis factor (TNF) and inducible nitric oxide synthase (iNOS) were decreased in brain hemorrhage sites after cell administration, and TUNEL-positive cells, which reflect cell death, were reduced. In an additional experiment, simultaneous administration of TNFα during administration of amnion-derived MSCs attenuated the effect of amnion-derived MSCs on the reduction of TUNEL-positive cells. This suggests that the inhibitory effect of amnion-derived MSCs on TNFα may be one of the possible mechanisms.
Free Research Field	脳神経外科、脳血管障害の外科治療、神経再生の基礎研究
Academic Significance and Societal Importance of the Research Achievements	脳出血に対して、現在有効な機能改善の治療法は継続的なリハビリテーションしかなく、今回羊膜由来MSCをマウス脳出血モデルへ静脈投与をすることで機能改善効果が確認できた。この細胞はすでに、他の疾患で人の臨床治験でに用いる細胞治療剤として品質管理されており、解凍することですぐに使用できるよう冷凍保存されている。よって、今後、脳出血患者への臨床試験を準備する段階である。このことは学術的ならび社会的意義が非常に大きい成果である。