| Project/Area Number |
17590161
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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 |
MORI Dezawa 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)
HOSHINO Mikio Kyoto University Graduate School of Medicine, Research Associate, 医学研究科, 助手 (70301273)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2005: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Keywords | Mesenchymal stem cell / Parkinson's disease / spinal cord injury / Muscle dystrophy / Regenerative medicine / Transplantation / Cvtokine / Trans differentiation / 分化転換 / 間葉系幹細胞 / 神経誘導 / 骨格筋幹細胞 / 間葉系細胞 / 神経変性疾患 |
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| Research Abstract |
Bone marrow stromal cells (MSCs) have the capability under specific conditions to differentiate into various cell types, such as osteocytes, chondrocytes and adipocytes. Here we demonstrate a highly efficient and specific induction of Schwann cells (peripheral glial cells), neurons and skeletal muscle cells from both rat and human MSCs.
Neuronal induction could be achieved by NICD transfection followed by trophic factor administration of bFGF+ CNTF + forskolin. MSCs expressed markers related to neural stem cell and neuronal progenitor cells after transfection with NICD, and subsequent administration of trophic factors induced post-mitotic neurons without differentiation of glial cells. Some of induced cells showed action potentials compatible with characteristics of functional neurons. Further treatment of the neurons with GDNF increased the proportion of dopamine-producing cells and transplantation of these neurons showed improvement in rat model of Parkinson's disease. Highly efficient skeletal muscle induction could also be achieved by the administration of a combination of cytokines followed by NICD transfection. Induced cells differentiate into muscle fibers upon transplantation into degenerated muscles. Since induced cells contained satellite-like cells, they contributed to subsequent regeneration upon repetitive damage without additional transplantation of cells.
Since our induction system does not depend on a rare stem cell population, but can utilize the general population of MSCs which can be easily isolated and expanded, functional Schwann cells, neurons and skeletal muscle cells can be obtained on a therapeutic scale. Our MSC differentiation system may contribute substantially to a major advance toward eventual cell-based therapies for neurodegenerative and muscle degenerative diseases.
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