| Project/Area Number |
13671492
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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 | Tokyo Medical and Dental University |
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Principal Investigator |
SHINOMIYA Kenichi Graduate School, Orthopaedic and Spinal Surgery, Professor, 大学院・医歯学総合研究科, 教授 (20111594)
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| Co-Investigator(Kenkyū-buntansha) |
ITOH Soichiro Division of Locomotorial Molecular Degeneration Research, Human Genes and Science Center, Associate Professor, 疾患遺伝子実験センター, 助教授 (10242190)
KOMORI Hiromichi Graduate School, Orthopaedic and Spinal Surgery, Associate Professor, 大学院・医歯学総合研究科, 助教授 (60262169)
OKABE Shigeo Graduate School, Anatomy and Cell Biology, Professor, 大学院・医歯学総合研究科, 教授 (60204012)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 2002: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2001: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | neural stem cell / peripheral nerve / transplantation / spinal cord regeneration / 細胞移動 / オリゴ・デンドロサイト |
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| Research Abstract |
Transplantation of in vitro-expanded neural stem cells (NSCs) is a potentially powerful tool to repair functions of the injured spinal cord. A prerequisite for the successful transplantation therapy is identification of optimized experimental parameters that can promote maximal survival, extensive migration, and selective differentiation of the transplanted NSC population in the spinal cord.
We evaluated the basic characteristics of NSC-like cells from two different donor sources, the embryonic hippocampus and spinal cord, after transplantation into the neonatal spinal cord. Proliferation and differentiation phenotypes of both NSC-like cells can be controlled by the concentration of the fibrobiast growth factor 2 (FGF2) in vitro. Both NSC-like cells can survive within the environment of the intact neonatal spinal cord and showed extensive migratory behavior shortly after transplantation. However, quantitative analysis revealed that 88% of total hippocampal cells were preferentially loca
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lized to the dorsal white matter. In contrast, only 64% of total spinal cord cells were in the dorsal white matter. Both NSC-like cells showed restricted phenotype toward the oligodendroglial lineage after transplantation. Transplantation of the mixture of two cell types revealed selective survival of hippocampus-derived NSC-like cells. BrdU proliferation assay revealed that 10% of total hippocampal cells and 7% of total spinal cord cells were immunoreactive with BrdU. A majority of progenitor cells migrated through dorsal white matter without proliferation during the period of one week after transplantation.
This study indicates the possibility of transplanting hippocampus-derived. NSCs to supply the cell source for immature oligodendrocytes, which are thought to be essential for both the myelination and trophic support of regenerating axons in the dorsal white matter of the spinal cord. A combination of hippocampus-derived NSC and peripheral nerves as scaffolds of the cells could be effective treatment to regenerate axons in injured spinal cord. Less
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