| Project/Area Number |
10671354
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | Mie University |
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Principal Investigator |
HIRATA Hitoshi Mie University, Hospital Lecturer, 医学部・附属病院, 講師 (80173243)
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| Co-Investigator(Kenkyū-buntansha) |
HIBASAMI Hiroshige Mie University, Faculty of Medicine, Professor, 医学部, 教授 (60024642)
山崎 隆 三重大学, 医学部, 助手 (70230399)
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| Project Period (FY) |
1998 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2000: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1999: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1998: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | Cultured Schwann cell / Apoptosis / Nerve Growth Factor / Nerve Growth Factor Receptor / Sphingomyelin Cycle / Antisense / Nerve Regeneration / Gene Therapy / シュワン細胞 / 移植 / 末梢神経 / 軸策再生 / 人工神経 / 神経再生 / ビュングナーバンド / ワーラー変性 |
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| Research Abstract |
Autologous nerve graft is a useful method which has a high axon growth promoting ability, however, the technique has a number of drawbacks including accompanying donor site mobidity and limited donor nerves available, which encourages the use of allogenic nerve graft. Although allogenic nerve graft under immunosuppressive therapy is as effective as autograft, withdrawal of immunosuppressive agents leads to Schwann cell loss and severe nerve degeneration. Theoretically, insidious replacement of rejected cells by autologous Schwann cells can prevent axonal degeneration. So, we try to develop an artificial nerve composed of both allogenic and autogenic Schwann cells and extracellular component. However it became apparent that cultured Schwann cells do not survive for a long period both in vivo and in vitro and are eliminated by apoptosis. We studied the mechanism behind Schwann cell death in peripheral nerve degeneration and regeneration and found that excessive coupling of nerve growth factor(NGF)and its low affinity receptor p75 NTR, although it is essential to propel Schwann cell cohlmn formation within the basal lamina, could induce Schwann cell apoptosis via sphingomyelin cycle and activation of NF-kB.The intensity of the signal was correlated to the expression levels of p75NTR by Schwann cells. The finding suggests that selective suppression of p75NTR expression by autologous Schwann cells can lead to selective elimination of allogenic Schwann cells. We have developed an antisense therapy for the purpose which can induce partial suppression of p75NTR expression in vitro and maintain the effect for a substantially long period both in vitro and in vivo. We made an artificial nerve containing autologous Schwann cells treated with the antisense and allogenic Schwann cells and have been studying the usefulness of the graft.
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