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Development of therapeutic strategy for Duchenne muscular dystrophy-Based on cell fusion and myogenic transdifferentiation theory

Research Project

Project/Area Number 19790749
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Pediatrics
Research InstitutionNational Research Institute for Child Health and Development

Principal Investigator

SAI Syoko  National Research Institute for Child Health and Development, 生殖・細胞医療研究部, 流動研究員 (80392497)

Project Period (FY) 2007 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥3,860,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2008: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2007: ¥1,000,000 (Direct Cost: ¥1,000,000)
Keywords筋ジストロフィー / 周産期幹細胞 / 幹細胞 / 骨格筋 / 細胞移植 / 筋ジストロフー
Research Abstract

Duchenne muscular dystrophy (DMD), the most common lethal genetic disorder in children, is an X-linked recessive muscle disease characterized by the absence of dystrophin at the sarcolemma of muscle fibers. We examined a putative mesenchymal stromal cells obtained from endometrial or placenta tissue samples to determine whether these cells repair muscular degeneration in a murine mdx model of DMD. Implanted cells conferred human dystrophin in degenerated muscle of immunodeficient mdx mice. We then examined endometrial-derived cells, menstrual blood-derived cells, and placenta-derived cell to determine whether primarily cultured nontransformed cells also repair dystrophied muscle. In vivo transfer of these cells into dystrophic muscles of immunodeficient mdx mice restored sarcolemmal expression of dystrophin. Labeling of implanted cells with enhanced green fluorescent protein and differential staining of human and murine nuclei suggest that human dystrophin expression is due to cell fusion between host myocytes and implanted cells. In vitro analysis revealed that cells can efficiently transdifferentiate into myoblasts/myocytes, fuse to C2C12 murine myoblasts by in vitro coculturing, and start to express dystrophin after fusion. These results demonstrate that the endometrial-derived cells, menstrual blood-derived cells, and placenta-derived cell can transfer dystrophin into dystrophied myocytes through cell fusion and transdifferentiation in vitro and in vivo.

Report

(4 results)
  • 2009 Annual Research Report   Final Research Report ( PDF )
  • 2008 Annual Research Report
  • 2007 Annual Research Report
  • Research Products

    (10 results)

All 2010 2008 2007

All Journal Article (9 results) (of which Peer Reviewed: 2 results) Presentation (1 results)

  • [Journal Article] Cells of extraembryonic mesodermal origin confer human dystrophin in the mdx model of Duchenne Muscular Dystrophy.2010

    • Author(s)
      Kawamichi Y, Cui CH*, Yoyoda M, Makino H, Takahashi Y, matsumoto K, Saito H, Ohta H, Saito K, Umezawa A.
    • Journal Title

      J Cell Physiol. 223(3)

      Pages: 695-702

    • Related Report
      2009 Final Research Report
  • [Journal Article] Novel Cardiac Precursor-Like Cells from Human Menstrual Blood-Derived Mesenchymal Cells.2008

    • Author(s)
      Hida N, Nishiyama N, Miyoshi S, Kira S, Segawa K, Uyama T, Mori T, Miyado K, Ikegami Y, Cui CH, Kiyono T, Kyo S, Shimizu T, Okano T, Sakamoto M, Ogawa S, Umezawa A.
    • Journal Title

      Stem Cells. 26(7)

      Pages: 1695-1704

    • Related Report
      2009 Final Research Report
  • [Journal Article] Myogenic transdifferentiation of menstrual blood-derived cells.2007

    • Author(s)
      Toyoda M, Cui CH, Umezawa A.
    • Journal Title

      Acta Myol. 26(3)

      Pages: 176-8

    • Related Report
      2009 Final Research Report
  • [Journal Article] Working' cardiomyocytes exhibiting plateau action potentials from human placenta-derived extraembryonic mesodermal cells.2007

    • Author(s)
      Okamoto K, Miyoshi S, Toyoda M, Hida N, Ikegami Y, Makino H, Nishiyama N, Tsuji H, Cui CH, Segawa K, Uyama T, Kami D, Miyado K, Asada H, Matsumoto K, Saito H, Yoshimura Y, Ogawa S, Aeba R, Yozu R, Umezawa A.
    • Journal Title

      Exp Cell Res. 313(12)

      Pages: 2550-2562

    • Related Report
      2009 Final Research Report
  • [Journal Article] Myogenesis by Endometrium derived Cells.2007

    • Author(s)
      Cui CH, Umezawa A.
    • Journal Title

      Medical Technology. 35

      Pages: 10-11

    • Related Report
      2009 Final Research Report
  • [Journal Article] Menstrual blood-derived cells confer human dystrophin expression in the murine model of Duchenne muscular dystrophy via cell fusion and myogenic transdifferentiation.2007

    • Author(s)
      Cui CH, Uyama T, Miyado K, Terai M, Kyo S, Kiyono T, Umezawa A.
    • Journal Title

      Mol Biol Cell. 18(5)

      Pages: 1586-1594

    • Related Report
      2009 Final Research Report
  • [Journal Article] Working cardiomyocytes exhibiting plateau action potentials from human placenta-derived extraembryonic mesodermal cells2007

    • Author(s)
      Okamoto K, Miyoshi S, Toyoda M, Hida N, I kegami Y, Makino H, Nishiyama N, Tsuji H, Cui CH, Segawa K, Uyama T, Kami D, Miyado K, Asada H, Matsumoto K, Saito H, Yoshimura Y, Ogawa S, Aeba R, Yozu R, Umezawa A
    • Journal Title

      Experimental cell research 15

      Pages: 2550-2562

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Menstrual blood-derived cells confer human dystrophin expression in the murine model ofDuchenne muscular dystrophy via cell fusion and myogenic transdifferentiation2007

    • Author(s)
      Cui CH, Uyama T, Miyado K, Terai M, Kyo S, Kiyono T, Umezawa A
    • Journal Title

      Molecular Biology of the Cell 18

      Pages: 1586-1594

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 子宮内膜細胞による骨格筋再生2007

    • Author(s)
      崔 昌浩、梅澤 明弘
    • Journal Title

      Medical Technology 35

      Pages: 666-667

    • Related Report
      2007 Annual Research Report
  • [Presentation] 子宮内膜細胞による骨格筋再生2007

    • Author(s)
      崔 昌造、梅澤 明弘
    • Organizer
      第28回日本炎症・再生医学会
    • Place of Presentation
      東京
    • Year and Date
      2007-08-02
    • Related Report
      2007 Annual Research Report

URL: 

Published: 2007-04-01   Modified: 2016-04-21  

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