Project/Area Number |
10557158
|
Research Category |
Grant-in-Aid for Scientific Research (B).
|
Allocation Type | Single-year Grants |
Section | 展開研究 |
Research Field |
Plastic surgery
|
Research Institution | Mie University |
Principal Investigator |
HIRATA Hitoshi Mie University, Hospital, Lecturer, 医学部・附属病院, 講師 (80173243)
|
Co-Investigator(Kenkyū-buntansha) |
NAGAI Hiroshi KOKEN BIO SCIENCE, Director, 所長 (90013812)
HIBASAMI Hiroshige Mie University, Faculty of Medicine, Professor, 医学部, 教授 (60024642)
|
Project Period (FY) |
1998 – 2000
|
Project Status |
Completed (Fiscal Year 2000)
|
Budget Amount *help |
¥13,500,000 (Direct Cost: ¥13,500,000)
Fiscal Year 2000: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1999: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1998: ¥10,400,000 (Direct Cost: ¥10,400,000)
|
Keywords | Artificial nerve / Schwann cell / Antisense / Nerve Growth Factor / Apoptosis / Nerve Regeneration / 末梢神経再生 / シユワン細胞 / ビュングナーバンド |
Research Abstract |
The purpose of the present study is to develop a hybrid artificial nerve which is composed of cultured Schwann cells and extacellular matrix component. We successfully established a method to obtain Schwann cells from peripheral nerves of adult animals with high purity and efficiently expand the population in vitro. However it became apparent that cultured Schwann cells do not survive for long both in vivo and in vitro and eliminated by apoptosis. So, we studied the mechanism behind Schwann cell death in peripheral nerve degeneration and regeneration. We have found that excessive coupling of nerve growth factor(NGF)and its low affinity receptor p75 NTR, although it is essential to propel Schwann cell column 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. These findings suggest that promotion and maintenance of Schwann cell columns within the scaffold made of extracellular matrix component can be achieved by keeping transcription level of the receptor by Schwann cells at low levels. So, we have explored the possibility of antisense therapy for the purpose. So far, we have succeeded in maintaining Schwann cell columns for a long time while keeping their high axonal growth promoting ability in vitro.
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