Résumé :
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Communication n° 321 We have previously developed a murine model of bone marrow (BM) transplantation from B6-TgGFP transgenic mice to normal irradiated B6 mice, the cytoplasmic green fluorescent protein (GFP) being used as an unambiguous marker of donor-derived cells in host muscle. Using this model we were able to demonstrate that stem cell marker-expressing cells found in connective tissue and myogenic precursor cells (satellite cells) may be derived from bone-marrow in adulthood. To investigate the therapeutic potential of BM transplantation in muscle diseases such as dystrophinopathies, we compare the results obtained in C57Bl6 recipient and Dmdmdx-4Cv recipient (mdx), a model for Duchenne muscular dystrophy in which muscle regeneration is dramatically increased. In mdx muscle compared with B6 muscle, we observed numerous GFP+ mononucleated cells corresponding to macrophages and numerous necrotic fibers filled by GFP+ macrophages and myoblasts. The number of GFP+ satellite cells number was similar in mdx and B6 mice 6 months post transplantation. However, GFP+ muscle fibers are more numerous in MDX mouse. They are already observed 1 month post transplantation whereas any GFP+ fiber could be detected at this time in B6 recipient. Six months post transplantation, we observed 4 folds more GFP+ muscle fiber in mdx mice than in B6 mice. Surprisingly, we observed few colocalization between GFP and dystrophin on serial cross sections. Therefore, we investigate the nuclear domain of dystrophin to demonstrate that it is clearly shorter than GFP nuclear domain.
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