| Project/Area Number |
15590166
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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 |
General anatomy (including Histology/Embryology)
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| Research Institution | Kyoto University |
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Principal Investigator |
DEZAWA Mari Kyoto University, Graduate School of Medicine, Associate Professor, 医学研究科, 助教授 (50272323)
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| Co-Investigator(Kenkyū-buntansha) |
KANNO Hiroshi Yokohama City University, School of Medicine, Associate Professor, 医学部, 助教授 (40244496)
IDE Chizuka Kyoto University, Graduate School of Medicine, Professor, 医学研究科, 教授 (70010080)
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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 |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2004: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2003: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | mesenchymal cell / Parkinson's disease / spinal cord injury / muscle dystrophy / regenerative medicine / transplantation / cytokine / transdifferentiation / 間葉系幹細胞 / 分化転換 / 神経分化 / グリア細胞 / 骨格筋 |
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| Research Abstract |
Bone marrow stromal cells (MSCs) have the capability under specific conditions to differentiate into other cell types. In this study, we demonstrate a highly efficient and specific induction of cells with neuronal, Schwann cells and skeletal muscle characteristics.
Neurons : MSCs were transfected with Notch intracellular domain(NICD) followed by cytokine treament. (bFGF+CNTF+forskolin). Induced neuronal cells expression neuronal markers, and showed voltage-gated fast sodium and action potentials. Glial markers could not be detected. Further treatment of the induced neuronal cells with GDNF increased the proportion of tyrosine hydroxylase (TH)-positive cells. Transplantation of these GDNF-treated cells showed improvement in apomorphine-induced rotational behavior, following intrastriatal implantation in a 6-hydroxy dopamine rat model of Parkinson's disease.
Schwann cells : Cells were treated with beta-mercaptoethanol and retinoic acid, followed by treatment with cytokines of bFGF, FSK, PD
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GF and neuregulin. MSCs changed their morphology after treatment with expression of Schwann cell markers of p75, GFAP, S-100 and P0. Transplantation of induced cells improved the function of spinal cord contusion injury model rats.
Skeletal muscle cells : MSCs were treated with cytokines (FSK+bFGF+PGDF+neuregulin) followed by NICD transfection. Induced cells expressed MyoD, Myogenin and other skeletal muscle markers and Pax7, c-MetR satellite cell markers, and formed multinuclear skeletal muscle cells. After intravenous transplantation of induced cell, muscle regeneration and integration of induced cells could be observed in mdx-mice (muscle dystrophy model mice).
MSCs have a great potential as therapeutic agents against neurological diseases since they can be readily obtained through a well-established clinical procedure and are easy to isolate and expand for autotransplantation with no risk of rejection. This study shows that a population of neuronal cells can be specifically generated from MSCs and that induced cells may allow for a neuroreconstructive approach. Less
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