4.4 Article

Human first-trimester chorionic villi have a myogenic potential

Journal

CELL AND TISSUE RESEARCH
Volume 348, Issue 1, Pages 189-197

Publisher

SPRINGER
DOI: 10.1007/s00441-012-1340-9

Keywords

Duchenne muscular dystrophy; First-trimester chorionic villi; Myogenic differentiation; Dystrophin; Cell therapy

Categories

Funding

  1. Ministry of Health, Labour and Welfare [20B-13-03]
  2. Research Committee of Spinal Muscular Atrophy (SMA) from the Ministry of Health, Labour and Welfare of Japan
  3. Global COE program
  4. Multidisciplinary Education and Research Center for Regenerative Medicine (MERCREM) from the Ministry of Education, Culture, Sports Science, and Technology (MEXT), Japan

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First-trimester chorionic-villi-derived cells (FTCVs) are the earliest fetal material that can be obtained for prenatal diagnosis of fetal disorders such as Duchenne muscular dystrophy (DMD). DMD is a devastating X-linked disorder characterized by the absence of dystrophin at the sarcolemma of muscle fibers. Currently, a limited number of treatment options are available for DMD, although cell therapy is a promising treatment strategy for muscle degeneration in DMD patients. A novel candidate source of cells for this approach is FTCVs taken between the 9th and 11th weeks of gestation. FTCVs might have a higher undifferentiated potential than any other tissue-derived cells because they are the earliest fetal material. We examined the expression of mesenchymal stem cell and pluripotent stem cell markers in FTCVs, in addition to their myogenic potential. FTCVs expressed mesenchymal stem cell markers and Nanog and Sox2 transcription factors as pluripotent stem cell markers. These cells efficiently differentiated into myotubes after myogenic induction, at which point Nanog and Sox2 were down-regulated, whereas MyoD, myogenin, desmin and dystrophin were up-regulated. To our knowledge, this is the first demonstration that FTCVs can be efficiently directed to differentiate in vitro into skeletal muscle cells that express dystrophin as the last stage marker of myogenic differentiation. The myogenic potential of FTCVs reveals their promise for use in cell therapy for DMD, for which no effective treatment presently exists.

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