2004 Fiscal Year Final Research Report Summary
The reset and transdifferentiation of bone marrow stromal cells and developmental research for organ regeneration
| 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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| Keywords | mesenchymal cell / Parkinson's disease / spinal cord injury / muscle dystrophy / regenerative medicine / transplantation / cytokine / transdifferentiation |
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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
… More
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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Research Products
(34 results)
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[Journal Article] Specific induction of neuronal cells from bone-marrow stromal cells and application for autologous transplantation2004
Author(s)
Dezawa M, Kanno H, Hoshino M, Cho H, Matsumoto N, Itokazu Y, Tajima N, Yamada H, Sawada H, Ishikawa H, Mimura T, kitada M, Suzuki Y, Ide C
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Journal Title
J Clin Invest 113
Pages: 1701-1710
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Tlx, an Orphan Nuclear Receptor, is Critical for the Control of Cell Numbers and Astrocyte Development in the Developing Retina.2004
Author(s)
Miyawaki T, Uemura A, Dezawa M, Yu S, Ide C, Nishikawa S, Honda Y, Tanabe Y, Tanabe T
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Journal Title
J Neurosci 24
Pages: 8124-8134
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Implantation of neural stem cells via cerebrospinal fluid into the injured root.2004
Author(s)
Ohta M, Suzuki Y, Noda T, Kataoka K, Chou H, Ishikawa N, Kitada M, Matsumoto N, Dezawa M, Suzuki S, Ide C
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Journal Title
NeuroReport 15
Pages: 1249-1253
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Bone marrow stromal cells infused into the cerebrospinal fluid promote functional recovery of the injured rat spinal cord with reduced cavity formation.2004
Author(s)
Ohta M, Suzuki Y, Noda T, Ejiri Y, Dezawa M, Kataoka K, Chou H, Matsumoto N, Iwashita Y, Mizuta E, Kuno S, Ide C
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Journal Title
Exp Neurol 187
Pages: 266-278
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Specific induction of neuronal cells from bone-marrow stromal cells and application for autologous transplantation.2004
Author(s)
Dezawa M, Kanno H, Hoshino M, Cho H, Matsumoto N, Itokazu Y, Tajima N, Yamada H, Sawada H, Ishikawa H, Mimura T, Kitada M, Suzuki Y, Ide C
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Journal Title
J.Clin.Invest. 113
Pages: 1701-1710
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Tlx, an Orphan Nuclear Receptor, is Critical for the Control of Cell Numbers and Astrocyte Development in the Developing Retina.2004
Author(s)
Miyawaki T, Uemura A, Dezawa M, Yu S, Ide C, Nishikawa S, Honda Y, Tanabe Y, Tanabe T.
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Journal Title
J Neurosci. 24
Pages: 8124-8134
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Implantation of neural stem cells via cerebrospinal fluid into the injured root.2004
Author(s)
Ohta M, Suzuki Y, Noda T, Kataoka K, Chou H, Ishikawa N, Kitada M, Matsumoto N, Dezawa M, Suzuki S, Ide C
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Journal Title
Neuro Report 15
Pages: 1249-1253
Description
「研究成果報告書概要(欧文)」より
-
[Journal Article] Bone marrow stromal cells infused into the cerebrospinal fluid promote functional recovery of the injured rat spinal cord with reduced cavity formation2004
Author(s)
Ohta M, Suzuki Y, Noda T, Ejiri Y, Dezawa M, Kataoka K, Chou H, Matsumoto N, Iwashita Y, Mizuta E, Kuno S, Ide C
-
Journal Title
Exp Neurol. 187
Pages: 266-278
Description
「研究成果報告書概要(欧文)」より
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