Résumé :
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Mesoangioblasts are recently characterized progenitor cells associated with the vasculature and able to differentiate in different types of solid mesoderm including skeletal muscle. Human adult mesoangioblasts were recently isolated and expanded in vitro from muscle biopsies: they were shown to correspond to a subset of human pericytes and, more importantly to differentiate spontaneously in skeletal muscle with high efficiency. This reflected an endogenous program of muscle pericytes which naturally contribute to post-natal growth of skeletal muscle as revealed by genetic lineage tracing using a pericyte specific promoter. When both wild type or dystrophic, genetically corrected, mesoangioblasts were delivered intra-arterially to dystrophic muscle of alpha-sarcoglycan null mice (a model for limb girdle muscular dystrophy), or they resulted in morphological and functional amelioration of the dystrophic phenotype. Intra-arterial or systemic delivery of wild type, non DLA matched mesoangioblasts in Golden Retriever dystrophic dogs resulted in a partial recovery of muscle morphology and function, dystrophin expression and clinical amelioration. Delivery of autologous mesoangioblasts expressing human micro-dystrophin did not cause a comparable amelioration, despite widespread micro-dystrophin expression. These results show efficacy of cell therapy in a large, immune-competent animal and set the rationale for a future clinical trial, using donor cells from an HLA-matched donor under immune suppression. Problems still facing this approach and possible strategies to overcome them will be discussed. Finally, an experimental strategy to stimulate angiogenesis and reduce connective tissue deposition in old dystrophic muscle to be then transplanted intra-arterially with mesoangioblasts will be presented.
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