Résumé :
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Myoblast transplantation in clinical trials is based on intramuscular injection of a population of muscle-derived cells. Up to date, homogeneity of this population throughout culture has been evaluated using the CD56 marker. According to our data, the CD56 population contains stem cells able to give rise to adipocytes in vitro. Differentiation of stem cells after transplantation into muscles is driven towards the myogenic lineage. However, adipocyte accumulation is observed in human dystrophic muscular diseases and likely, stem cells transplanted in a muscle environment permissive to fat development may be committed towards adipogenesis at the expense of myogenesis. Therefore, for muscular cell therapy, it is critical to identify a cell population with a high myogenic and a low adipogenic potential from the mixture of cells to be transplanted. The stem cell marker CD34 allowed us to sort two distinct populations from human pediatric and adult muscle biopsies. In vitro, the CD34+ cells were myogenic and adipogenic whereas the CD34- cells were only myogenic. Both cell populations have muscle regeneration potential after transplantation in cryo-injuried muscle of immunodeficient Rag2-/- ?c-/- mice. To our knowledge, there is no convenient mouse model fully mimicking human muscular dystrophies, i.e. fat infiltration in regenerative muscles. However, we have observed a higher fat development in cryo-injured tibialis anterior muscle of Rag2/gc-/- mice when using clodronate-containing liposomes. Therefore, experiments are carrying out to determine the fate of CD34 cell populations after their muscle transplantation in this new mouse model having a micro-environment permissive for differentiation of transplanted cells into adipocytes. In conclusion, the muscle CD34 negative cell population could represent a new alternative cell population in cell therapy of muscular dystrophy.
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