Project/Area Number |
09671434
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Cerebral neurosurgery
|
Research Institution | Sapporo Medical University School of Medicine , Department of Neurosurgery |
Principal Investigator |
UEDA Teiji Sapporo Medical University, Sch. Of Med, Dept. Of Neurosurgery, Asso. Prof.., 医学部, 助教授 (90160184)
|
Co-Investigator(Kenkyū-buntansha) |
HONMOU Osamu Sapporo Medical University, Sch. Of Med, Dept. Of Neurosurgery, Senior instructor, 医学部, 助手 (90285007)
|
Project Period (FY) |
1997 – 1999
|
Project Status |
Completed (Fiscal Year 1999)
|
Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 1999: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1998: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1997: ¥1,700,000 (Direct Cost: ¥1,700,000)
|
Keywords | axon / demyelination / gene / transplantation / stem cell / transporter |
Research Abstract |
It has generally been assumed that the adult central nervous system (CNS) is incapable of significant self-repair because of a lack of neurogenesis in the adult mammalian CNS. Although we have reported that remyelination of demyelinated CNS axons occurs following transplantation of exogenous glial cells in the animal models, it is still unclear whether transplantation of myelin-forming cell derived from adult humans can remyelinate the demyelinated axons and restore the conduction properties in the adult CNS. To examine this issue, the dorsal columns of the adult rat spinal cord were demyelinated by X-irradiation and intraspinal infections of ethidium bromide. Cell suspensions of myelin-forming cells such as Schwann cells, olfactory ensheathing cells, neural stem cells derived from adult humans were infected into the glial-free lesion site. Light and electron microscopic examination of the dorsal columns revealed cells engaging and myelinating axons in the demyelinated regions 21 days
… More
after transplantation. In addition, in situ hybridization study with COT-1 DNA probe which is specific to human DNA indicated that the new myelin was formed by the human cells. The dorsal columns were removed and maintained in an in vitro recording chamber; conduction properties were studied using field potential recording techniques. The demyelinated axons exhibited conduction slowing and block, and a reduction in their ability to follow high frequency stimulation. Axons remyelinated by transplantation of myelin-forming cells derived from adult human exhibited restoration of conduction through the lesion, with re-establishment of normal conduction velocity. The axons remyelinated following transplantation showed enhanced impulse recovery to paired pulse stimulation and greater frequency-following capability as compared to both demyelinated axons. These results demonstrate the functional repair of demyelinated axons in the adult CNS by transplantation of myelin-forming cells derived from adult human. Less
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