Characterization of Dystrophin expressing mesoangioblasts fate after their transplantation in dystrophic muscles. Identification of differentiation lineages of mesoangioblasts upon transplantation. Discovery of signaling pathways improving their capacity to differentiate toward myogenic lineage.

Duchenne muscular dystrophy (DMD) is a lethal muscle-wasting disease caused by the lack of dystrophin in muscle fibres which is currently without curative treatment. Mesoangioblasts (MABs) are multipotent progenitor cells that can differentiate to a myogenic lineage and that can be used to express Dystrophin upon transplantation into to muscles, in autologous gene therapy approaches. However, their fate in the muscle environment remains poorly characterized, as most cells may not undergo a myogenic differentiation path, which limits their capacity to restore dystrophin expression into transplanted muscles. Here, we investigated the fate of MABs following their transplantation in DMD murine muscles using a mass cytometry strategy and characterized various MABs differentiation lineages once inside the muscle environment. This allowed the identification and isolation of a fraction of MAB-derived cells presenting common properties with satellite muscle stem cells. We assessed cytokine and growth factor signaling pathways agonists, and identified a combination of such signals that ameliorates MABs capacity to undergo myogenic differentiation and to restore dystrophin expression upon engraftment in myopathic murine muscles.