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Basic study for regenerative medicine in muscular dystrophy by bone marrow transplantation

Research Project

Project/Area Number 16590856
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurology
Research InstitutionKawasaki Medical School

Principal Investigator

HAGIWARA Hiroki  Kawasaki Medical School, Neurology, Assistant Professor, 医学部, 講師 (80276732)

Co-Investigator(Kenkyū-buntansha) MURAKAMI Tatsufumi  Kawasaki Medical School, Neurology, Associate Professor, 医学部, 助教授 (30330591)
SUNADA Yoshihide  Kawasaki Medical School, Neurology, Professor, 医学部, 教授 (00240713)
TESHIMA Takanori  Kyushu University Hospital, Center for Cellular and Molecular Medicine, Associate Professor, 医学部, 助教授 (40284096)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥2,200,000 (Direct Cost: ¥2,200,000)
Keywordsbone marrow transplantation / muscular dystrophy / regenerative medicine / EGFP mouse / dy mouse / mdx moude / extracellular matrix / laminin
Research Abstract

To evaluate the therapeutic potential of bone marrow, we examined whether pathogenesis in dystrophin-deficient (mdx) mice (a model for Duchenne muscular dystrophy [DMD]) and laminin alpha2-deficient (dy) mice (a model for congenital muscular dystrophy type 1A [MDC1A]) is ameliorated by bone marrow transplantation. We selected whole bone marrow cells for transplantation. Green fluorescent protein (GFP) mice were used as donors. Both model mice exhibited GFP-positive muscle fibers. In mdx mice, bone marrow transplantation failed to produce any significant differences in muscle pathology, although some GFP-positive fibers with restored dystrophin expression were observed. In contrast, in the dy mice, bone marrow transplantation led to a significant increase in lifespan and an increase in growth rate, muscle strength, and respiratory function. We conclude that bone marrow transplantation improved outcome in dy mice but not mdx mice. It is possible that bone marrow transplantation therapies designed to ameliorate muscular dystrophies are more likely to succeed in MDC1A than in DMD. Our results would open up the direct clinical application of bone marrow transplantation for muscular dystrophies such as MDC1A.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (21 results)

All 2005 2004 Other

All Journal Article (20 results) Book (1 results)

  • [Journal Article] 筋ジストロフィーモデルマウスに対する骨髄移植法の治療効果の検討2005

    • Author(s)
      萩原宏毅
    • Journal Title

      臨床神経学 45

      Pages: 1136-1136

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] ミオスタチンプロドメインによる変異カベオリン3トランスジェニックマウス表現型改善2005

    • Author(s)
      大澤裕
    • Journal Title

      臨床神経学 45

      Pages: 1196-1196

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 筋ジストロフィーモデルマウスに対する骨髄移植療法の治療効果の検討2005

    • Author(s)
      砂田芳秀
    • Journal Title

      平成17年度厚生労働省精神・神経疾患研究委託費「筋ジストロフィーおよびその関連する疾患の病態生理の解明と治療薬物の開発に関する研究」清水班班会議録

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Caveolin-3によるmyostatin signalの制御2005

    • Author(s)
      砂田芳秀
    • Journal Title

      平成17年度厚生労働省精神・神経疾患研究委託費「筋ジストロフィーおよびその関連する疾患の病態生理の解明と治療薬物の開発に関する研究」清水班班会議録

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Reduced amplitude of the sural nerve sensory action potential in PARK2 patients2005

    • Author(s)
      Ohsawa Y
    • Journal Title

      Neurology 65

      Pages: 459-462

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Regulation of myostatin signaling by caveolin-32005

    • Author(s)
      Sunada Y
    • Journal Title

      International Workshop Abstracts ; Japan Muscular Dystrophy Research Council

      Pages: 15-15

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Skeletal muscle hyperplasia in the transgenic mice overexpressing the myostatin prodomain2004

    • Author(s)
      Hagiwara H
    • Journal Title

      Neuromuscular Disorders 14(8-9)

      Pages: 610-610

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Restoration of a myopathic phenotype of mutant caveolin-3 transgenic mice by crossing with mutant myostatin transgenic mice2004

    • Author(s)
      Ohasawa Y
    • Journal Title

      Neuromuscular Disorders 14(8-9)

      Pages: 610-610

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Overexpression of P104L mutant caveolin-3 mice develops hypertrophic cardiomyopathy with enhanced contractility2004

    • Author(s)
      Ohasawa Y
    • Journal Title

      Human Molecular Genetics 13(2)

      Pages: 151-157

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 新ししジストロフィン結合蛋白複合体の細胞外リガンドーバイグリカン2004

    • Author(s)
      萩原宏毅
    • Journal Title

      臨床神経学 44

      Pages: 1161-1161

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Skeletal muscle hyperplasia in the transgenic mice overexpressing the myostatin prodomain.2004

    • Author(s)
      Hagiwara H, Ohsawa Y, Sasano S, Nishi M, Yasue A, Noji S, Sunada Y.
    • Journal Title

      Neuromuscular Disorders 14(8-9)

      Pages: 610-610

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Restoration of a myopathic phenotype of mutant caveolin-3 transgenic mice by crossing with mutant myostatin transgenic mice.2004

    • Author(s)
      Ohsawa Y, Hagiwara H, Sasano S, Nishi N, Yasue A, Noji S, Sunada Y.
    • Journal Title

      Neuromuscular Disorders 14(8-9)

      Pages: 610-610

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Overexpression of P104L mutant caveolin-3 in mice develops hypertrophic cardiomyopathy with enhanced contractility in association with increased endothelial nitric oxide synthase activity.2004

    • Author(s)
      Ohsawa Y, Toko H, Katsura M, Morimoto K, Yamada H, Ichikawa Y, Murakami T, Ohkuma S, Komuro I, Sunada Y.
    • Journal Title

      Hum Mol Genet. 13(2)

      Pages: 151-157

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Skeletal muscle hyperplasia in the transgenic mice overexpressing the myostatin prodomain.2004

    • Author(s)
      Hagiwara H
    • Journal Title

      Neuromuscular Disorders 14(8-9)

      Pages: 610-610

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Restoration of a myopathic phenotype of mutant caveolin-3 transgenic mice by crossing with mutant myostatin transgenic mice.2004

    • Author(s)
      Ohsawa Y
    • Journal Title

      Neuromuscular Disorders 14(8-9)

      Pages: 610-610

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Overexpression of P104L mutant caveolin-3 in mice develops hypertrophic cardiomyopathy with enhanced contractility2004

    • Author(s)
      Ohsawa Y
    • Journal Title

      Hum Mol Genet. 13(2)

      Pages: 151-157

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 新しいジストロフィン結合蛋白複合体の細胞外リガンド-バイグリカン2004

    • Author(s)
      萩原宏毅
    • Journal Title

      臨床神経学 44

      Pages: 1161-1161

    • Related Report
      2004 Annual Research Report
  • [Journal Article] スタチン関連ミオパチー2004

    • Author(s)
      萩原宏毅
    • Journal Title

      JAMA 日本語版 3

      Pages: 108-118

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Biglycan targets dystrobrevin, syntrophin and nNOS to the muscle cell membrane

    • Author(s)
      Mercado ML
    • Journal Title

      FASEB Journal (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Biglycan targets dystrobrevin, syntrophin and nNOS to the muscle cell membrane.

    • Author(s)
      Mercado ML, Amenta AR, Hagiwara H, Rafii MS, Owens RT, McQuillan DJ, Froehner SC Fallon JR.
    • Journal Title

      FASEB Journal (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] 筋強直性ジストロフィー 今日の治療指針(山口徹, 北原光夫編)2005

    • Author(s)
      砂田芳秀
    • Publisher
      医学書院
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary

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Published: 2004-04-01   Modified: 2016-04-21  

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