Lionel O Mavoungou
University of Lausanne, Switzerland
Title: Characterization of mesoangioblasts and modulation of their engraftment capacity for Duchenne muscular dystrophy gene therapy
Biography
Biography: Lionel O Mavoungou
Abstract
Duchenne muscular dystrophy (DMD) is a lethal monogenic pathology characterized by progressive muscle degeneration. We designed a potential autologous gene therapy protocol based on the intra-muscular transplantation of dystrophic mdx mesoangioblasts (MABs) transfected with full length dystrophin using the piggyBac transposon system into mdx SCID mice. This approach allowed us to detect transplanted MAB-derived dystrophin expression in myofibers and a functional amelioration of the muscle function. Transplanted muscle analysis revealed different fates for MABs. Some fused with myofibers, while the fate of other cells remained unclear. In order to characterize these cell populations, a mass cytometry analysis was performed before and after MABs transplant. This revealed that a subpopulation deriving from the MABs, that we named MAB-SAT, express satellite cell markers. A transcriptome analysis of this MAB-SAT subpopulation revealed an identity intermediate to MABs and endogenous satellite cells. The characterization of other MAB fates revealed a diverse spectrum of differentiation paths after transplant which allows quantifying the proportion of MABs for each particular differentiation lineage. In parallel, we screened signaling pathways affecting satellite cell markers expression in MABs, allowing the identification of several signaling pathways that favor the expression of satellite cell markers in MABs before transplant, in attempts to enhance the MABs potential to engraft and differentiate into myogenic lineage when used in autologous cell therapy.