Differential analysis of dystrophic dog muscle after MuStem cell therapy

Duchenne Muscular Dystrophy (DMD), the most common form of inherited neuromuscular disorder, is caused by mutations in the dystrophin gene leading to progressive muscle loss. Secondary changes in signaling pathways and energy metabolism are aggravating factors. Thus, for the evaluation of novel therapeutic approaches, it is essential to analyse the reversal of both primary and secondary abnormalities in treated muscle. MuStem cells constitute a new progenitor cell population proposed as a source of cells for a therapeutic strategy. When injected in Golden Retriever Muscular Dystrophy (GRMD) dogs, MuStem cells contribute to myofiber regeneration, satellite cell replenishment, and dystrophin expression. This cell therapy leads to muscle damage course limitation with an increased regeneration activity and an interstitial expansion restriction, and persisting stabilization of the dog's clinical status. In this study, we used isotope-coded protein labeling (ICPL) to compare the protein expression profiles of muscles coming from three different types of dogs: healthy, GRMD and GRMD after injection of MuStem cells. Based on the comparison of three biological replicates, these triplex ICPL experiments led to the identification of proteins differentially expressed after treatment. This study contributes to a better understanding of the mechanisms of action of MuStem cells.