Résumé :
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Duchenne muscular dystrophy (DMD) is an X-linked muscle wasting disease caused by the absence of functional dystrophin at the sarcolemma. There is currently no therapy for this disease, but stem cell-based cell therapy, eventually in combination with gene therapy, is one of the therapeutic approaches that have been envisioned. Satellite cells are the major source of myogenic cells for physiological growth and regeneration of post-natal skeletal muscle. However since all muscles in the body are affected in DMD, this strategy may not be the ideal candidate due to the lack of dispersion of donor myoblasts. Results from clinical trials have suggested that the transplanted cells remain close to the injection site, thus limiting the clinical benefit of this strategy. Recently, we reported that human CD133+ cells migrated better than satellite cells when injected into regenerating muscle of immunodeficient mice. They also differentiated very efficiently into myofibers and also renewed the pool of satellite cells. CD133+ cells could thus be a better candidate for cell therapy.The Golden Retriever Muscular Dystrophy (GRMD) dogs have usually severe and progressive muscle weakness, very similar to that observed in DMD patients. We have compared the percentage of circulating CD133+ cells in both healthy and GRMD dogs. Blood samples were collected from dogs aged between 2 months and 1 year of age and were analyzed by flow cytometry. Cells expressing CD133 were detected in both healthy and GRMD dogs, although as a heterogeneous population. While the average percentage of CD133+ cells was highest at 4 months of age in control dogs, it remained almost constant from 2 months until 11 months in the GRMD dogs. The myogenic potential of these cells from GRMD dogs is now being evaluated in vitro.Financial support: Universiterre et Marie Curie (UPMC), CNRS, INSERM, University Paris 5, ANR-Genopath In-A-Fib, the Association Franse contre les Myopathies (AFM), AIM, MyoAge (EC 7th FP, contract 223576), CNPq, Capes and Fiocruz (Brazil). This work has been conducted in the framework of the Inserm/UPMC/Fiocruz International Associated Laboratory of Cell Therapy and Immunotherapy.
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