| Project/Area Number |
16K10729
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Neurosurgery
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| Research Institution | Nagasaki University |
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Principal Investigator |
HIU Takeshi 長崎大学, 医歯薬学総合研究科(医学系), 客員研究員 (00404260)
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| Co-Investigator(Kenkyū-buntansha) |
堀江 信貴 長崎大学, 病院(医学系), 講師 (70380912)
松尾 孝之 長崎大学, 医歯薬学総合研究科(医学系), 教授 (00274655)
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
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)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 脳梗塞 / 幹細胞移植 / シナプス / ミクログリア / 脂肪由来幹細胞 / 神経幹細胞 / synapse / peri-infarct area / 脳血管内治療 |
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| Outline of Final Research Achievements |
Vehicle or human neural progenitor cells (hNPCs) derived from fetal cortex were transplanted into the ischemic cortex of Nude rats at 7 days after distal middle cerebral artery occlusion. Transplantation of hNPCs significantly improved behavioral recovery after stroke compared to vehicle-treated rats at 3-4 weeks post-transplantation. We found that transplanted stem cells enhanced endogenous brain repair processes including structural brain plasticity. hNPC-treated rats had a higher density of glutamatergic synapses in layer 5 at 4 weeks posttransplantation, compared to vehicle-treated rats.
Next, we investigated the regenerative capacity of transplanted cells focusing on donor age for ischaemic stroke. Transplantation of young hMSC appears to provide better functional recovery through anti-inflammatory effects, vessel maturation, and neurogenesis potentially by the dominance of trophic factor secretion.
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| Academic Significance and Societal Importance of the Research Achievements |
グルタミン酸シナプスとGABA シナプスの定量化を行った. synapsinとPSDのcolocalizationのあるものをグルタミン酸 シナプスと定義した. 移植後4週間後に梗塞周辺部のシナプスの定量化を行い, グルタミン酸シナプスの増加を認めた. 一方でGABAシナプスは増加していなかった. この変化は移植1週間後には認めなかった. 機能回復が得られる移植4週間後にグルタミン酸シナプスの増加を認め, グルタミン酸シナプスが機能回復に寄与していることが示唆されin vitroでも同様に幹細胞によるシナプスの増加を認めた.
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