Differential Gene Expression Profiling of Dystrophic XXXX Muscle after MuStem Cell Transplantation.

@entity4094 @entity43573 @entity235 @entity3986 @entity1555 @entity460
BACKGROUND: Several adult stem cell populations exhibit myogenic regenerative potential, thus representing attractive candidates for therapeutic approaches of @entity4094 such as @entity1555 ( @entity1555 ). We have recently shown that systemic delivery of MuStem cells, skeletal muscle-resident stem cells isolated in healthy @entity235 , generates the remodelling of muscle tissue and gives rise to striking clinical benefits in @entity3986 ( @entity3986 ) @entity235 . This global effect, which is observed in the clinically relevant @entity1555 animal model, leads us to question here the molecular pathways that are impacted by MuStem cell transplantation. To address this issue, we compare the global gene expression profile between healthy, @entity3986 and MuStem cell treated @entity3986 @entity235 muscle, four months after allogenic MuStem cell transplantation. RESULTS: In the dystrophic context of the @entity3986 @entity235 , disease-related deregulation is observed in the case of 282 genes related to various processes such as inflammatory response, regeneration, @entity460 ion binding, extracellular matrix organization, metabolism and apoptosis regulation. Importantly, we reveal the impact of MuStem cell transplantation on several molecular and cellular pathways based on a selection of 31 genes displaying signals specifically modulated by the treatment. Concomitant with a diffuse @entity43573 expression, a histological remodelling and a stabilization of @entity3986 @entity235 clinical status, we show that cell delivery is associated with an up-regulation of genes reflecting a sustained enhancement of muscle regeneration. We also identify a decreased mRNA expression of a set of genes having metabolic functions associated with lipid homeostasis and energy. Interestingly, ubiquitin-mediated protein degradation is highly enhanced in @entity3986 @entity235 muscle after systemic delivery of MuStem cells. CONCLUSIONS: Overall, our results provide the first high-throughput characterization of @entity3986 @entity235 muscle and throw new light on the complex molecular/cellular effects associated with muscle repair and the clinical efficacy of MuStem cell-based therapy.
