| Project/Area Number |
15300114
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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 |
Nerve anatomy/Neuropathology
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| Research Institution | Kyoto University Graduate School of Medicine |
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Principal Investigator |
IDE Chizuka Kyoto University, Graduate School of Medicine, Department of Anatomy and Neurobiology, Professor, 医学研究科, 教授 (70010080)
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| Co-Investigator(Kenkyū-buntansha) |
SUZUKI Yoshihisa Kyoto University, Graduate School of Medicine, Department of Plastic and Reconstructive Surgery, Associate Professor, 医学研究科, 助教授 (30243025)
DEZAWA Mari Kyoto University, Graduate School of Medicine, Department of Anatomy and Neurobiology, Associate Professor, 医学研究科, 助教授 (50272323)
MATSUMOTO Naoya Kyoto University, Graduate School of Medicine, Department of Anatomy and Neurobiology, Research Associate, 医学研究科, 助手 (50359808)
菅野 洋 横浜市立大学, 医学部, 講師 (40244496)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥16,700,000 (Direct Cost: ¥16,700,000)
Fiscal Year 2004: ¥7,900,000 (Direct Cost: ¥7,900,000)
Fiscal Year 2003: ¥8,800,000 (Direct Cost: ¥8,800,000)
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| Keywords | bone marrow stromal cell / neural stem cell / cell transplantation / spinal cord injury / astrocyte / choroid plexus ependymal cell / intra-cerebrospinal fluid injection / BBB scale / 空洞 / 行動の恢復 / 栄養因子 / 急性期 / 髄液内移植 / 行動学的評価 / 組織的修復 / 細胞培養 |
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| Research Abstract |
Based on the early experiments, we recognized that there are big barriers for neural stem cells to be clinically applied : those are ethical problems concerning the use of fetus and inevitable allergenic transplantation. On the other hand, bone marrow stromal cells (BMSCs) have great advantages in being autogenic for clinical application. In experiments, BMSCs were injected into the cerebrospinal fluid (CSF) through the 4^th ventricle of the rat. Many injected BMSCs were attached to the spinal cord surface, and some of them further invaded the lesion. Based on the BBB scale, cell-graft rats showed 14 15 and 11 points in locomotion, while the controls were 10 and 8 points, in the mild and strong spinal cord crush, respectively. The size of spinal cord cavity was ca. 1/2 smaller in the cell-graft rats than the controls. Less proliferation of astrocytes was observed, and a larger amount of neural components was preserved in the cell-graft rats than in the controls.
Injected cells disappear
… More
ed from the spinal cord within 4-5 weeks after injection. This implies that injected BMSCs exerted their effects not by being integrated into the host tissue, but by releasing some trophic factors into the CSF. The in vitro experiments also supported this hypothesis. BMSCs function not as stem cells, but as ordinary somatic cells derived from adult animals. It is considered that BMSCs suppress the degenerative processes, and at the same time promote the survival, of injured cells at the early stage of degeneration. We confirmed the safety of BMSC injection into the CSF in the monkey by injecting autogenic BMSCs through lumbar puncture. We provided a complete protocol for clinical application, and the Ethic Committee of Kansai University approved this cell transplantation to patients with spinal cord therapy by BMSC transplantation to patients with spinal cord injury on July 1^<st> 2005. We are now ready for the BMSC transplantation therapy to patients matched to the protocol.
In parallel with this study, we also examined the effects of choroid plexus ependymal (epithelial) cells to the ischemic brain injury, and clarified that the injection of cultured choroid plexus ependymal cells have a great effect on the recovery of brain tissue from ischemic damages. This finding might open a new horizon for the therapy of ischemic brain injury. Less
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