Efficacy of C5a antagonist for human iPS-derived neural precursor cells transplanted into injured spinal cord
| Project/Area Number |
17H04318
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Orthopaedic surgery
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| Research Institution | Keio University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000)
Fiscal Year 2019: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
Fiscal Year 2018: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2017: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
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| Keywords | ヒトiPS細胞 / 神経幹細胞 / 細胞移植治療 / 補体 / 神経炎症 / 脊髄損傷 / C5aアンタゴニスト / 細胞移植 / iPS細胞 / 生着率 / 機能回復 / 補体抑制剤 / 神経前駆細胞 |
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| Outline of Final Research Achievements |
Because inflammatory reaction is intense at acute phase of spinal cord injury (SCI), cell transplantation therapy during this stage is not effective due to low survival rate of transplanted cells. In this study, by administrating complement receptor antagonist, transplanted human iPS cell-derived neural stem cells well survived and promoted motor functional recovery when grafted even at acute phase. The antagonist suppressed the expression of inflammatory cytokines, infiltration of inflammatory cells, and the apoptosis of neural cells in the spinal cord. This histological efficacy can contribute to making a favorable environment for the transplanted cells to survive. We believe that this study will lead to future clinical application as a treatment that enhances the effect of cell transplantation for SCI.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、脊髄損傷モデルに対してC5a受容体アンタゴニストを投与することにより、損傷急性期においても移植した神経幹細胞が生着し、運動機能が回復することを明らかにした。これまでの脊髄損傷における細胞移植治療は、炎症が収まる亜急性期での移植が有効とされているが、本研究により従来よりも早期の治療介入が可能になると考える。
C5aを阻害する薬剤は、臓器移植や神経変性疾患など臨床の現場で既に使用されている。本研究は、脊髄損傷に対する細胞移植の効果をより高める治療として、今後の臨床応用に繋がる研究成果と考える。
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Report
(4 results)
Research Products
(15 results)
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[Journal Article] A phase I/II study for intrathecal administration of recombinant human hepatocyte growth factor in patients with acute spinal cord injury: a double-blind, randomized clinical trial of safety and efficacy.2020
Author(s)
Nagoshi N, Tsuji O, Kitamura K, Suda K, Maeda T, Yato Y, Abe T, Hayata D, Matsumoto M, Okano H, Nakamura M.
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Journal Title
Journal of Neurotrauma
Volume: -
Related Report
Peer Reviewed
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[Journal Article] The adeno-associated virus rh 10 vector is an effective gene transfer system for chronic spinal cord injury2019
Author(s)
Hoshino Y, Nishide K, Nagoshi N, Shibata S, Moritoki N, Kojima K, Tsuji O, Matsumoto M, Kohyama J, Nakamura M, Okano H
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Journal Title
Scientific Reports
Volume: 9
Pages: 9844-9844
Related Report
Peer Reviewed
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