Résumé :
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Duchenne Muscular Dystrophy (DMD) is a progressive fatal X-linked recessive disorder of skeletal and cardiac muscles. It represents the most common muscular dystrophy, affecting one in 3,500 male births (Emery, 1991). It is characterized by the lack of dystrophin at the muscle fiber membrane (Hoffman et al., 1987) that results in fiber necrosis and progressive muscle weakness. Over the last decade, adult stem cells have received attention for their potential use in neuromuscular disease therapies (Farini et al., 2009; review). Here, we analyze a stem cell population isolated from healthy dog skeletal muscle based on its poor adherence properties and we demonstrate its ability to participate in myofiber repair when administrated to the dystrophic dog corresponding to the clinically relevant DMD model. These cells, that we name MuStem cells, display a large expansion capacity associated with high clonogenicity and atypical division modalities by generating two morphologically distinct cells. Phenotypically, MuStem cells correspond to early myogenic progenitors and uncommitted cells. When assayed in appropriate cell induction media, primary bulk cultures give rise to several cell types, revealing a multi-lineage differentiation potential. They contribute to myofiber regeneration, satellite cell replenishment and dystrophin-associated complex restoration. Importantly, their systemic delivery results in dystrophin expression, muscle tissue remodelling and dramatic clinical improvement. Clinical efficiency is observed in dystrophic dogs at least two years after the MuStem cell delivery. These data demonstrate that MuStem cells provide an attractive therapeutic avenue for DMD patients.
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