Résumé :
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Mesoangioblasts are recently characterized progenitor cells, associated with the vasculature and able to differentiate into different types of solid mesoderm, including skeletal muscle (Minasi et al. Development 129, 2773, 2002). When wild type or dystrophic, genetically corrected, mesoangioblasts were delivered intra-arterially to dystrophic muscle of a-sarcoglycan KO mice (a model for limb girdle muscular dystrophy), they resulted in a significant functional amelioration of the dystrophic phenotype (Sampaolesi et al. Science 301, 487, 2003). Intra-arterial delivery of wt mesoangioblasts, non DLA matched to GRMD 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 (Sampaolesi et al. Nature 444, 574, 2006). Human adult mesoangioblasts were isolated and expanded in vitro from muscle biopsies: they were shown to correspond to a subset of pericytes (Dellavalle et al. Nature Cell Biol. 9, 255, 2007). Based on these results, a monocenter, prospective, nonrandomised, clinical phase I/II study of cell therapy with HLA-matched donor human mesoangioblasts in DMD patients started in June 2009, with a one year preliminary study (involving 28 DMD patients, aged 5-10), required to validate outcome measures. Six out of these patients will undergo successive intra-arterial transplantations at escalating doses of cells under a continuous regime of immune suppression. Safety will be the primary objective of the study. A possible increase in muscle strength as a consequence of mesoangioblast transplantation will also be evaluated. Problems still facing this approach and possible strategies to overcome them will be discussed.This work is supported by grants from the European Community, the European Research Council, Duchenne Parent Project, Telethon, MDA, AFM and the Italian Ministries of Research and Health.
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