2002 Fiscal Year Final Research Report Summary
experimental study to enhance peripheral nerve regeneration by inhibiting the Schwann cell apoptosis using antisense
| Project/Area Number |
13470308
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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 | Mie University |
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Principal Investigator |
KASAI Yuichi Mie University, Hospital Research Associate, 医学部附属病院, 助手 (20242943)
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| Co-Investigator(Kenkyū-buntansha) |
HIRATA Hitoshi Mie University, Hospital Assistant Professor, 医学部附属病院, 講師 (80173243)
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| Project Period (FY) |
2001 – 2002
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| Keywords | Schwann Cell / Apoptosis / Nerve regeneratin / antisense / Nerve growth factor receptor |
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| Research Abstract |
We have identified p75NTR receptor as a regulator of phenotypic change of Schwann cells during wallerian degeneration and Schwann cell apoptosis in Schwann cell column atrophy. In this project, we tried to develop antisense therapy targeting the receptor to enhance both formation and maintainance of the Schwann cell column, structurally and functionally. We used two classes of antisense : phosphorothioate antisense and morpholino antisense. The inhibition of the receptor on the axons did not show any biological effect on the neuron. In contrast, it affected drastically on Schwann cell biology. Since phosphorothioate antisense induced rapid Schwann cell death due to its non-antisense cytotoxic effect even at 1ug/ml, the lowest concentration required to exert antisense effect. By contrast, morpholino antisense not only significantly enhanced Schwann cell survival but also promoted Schwann cell proliferation without any appreciable side effects. So, moripholino antisense can be a promising candidate for antisense therapy to enhance peripheral nerve regeneration. Due to the lack of effective in vivo delivery system for the antisense, our strategy at present is ex-vivo delivery to the cultured Schwann cell impregnated artifitial nerve constructed by elastin and collagen I.
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