The Role of Non-Myogenic Mesenchymal Stem Cells in Skeletal Muscle of Dystrophin/Utrophin Double Knockout Mice

摘要: Adult skeletal muscle possesses a remarkable regenerative ability, which largely depends on satellite cells; however, in severe muscular dystrophies, such as Duchenne dystrophy (DMD), integrity is compromised and the often replaced by mixture of fibrous tissue white adipocytes process termed fibro-adipogenic degeneration. The precise cellular origin environmental cues responsible for accumulation fat/fibrotic tissues during course disease remain unknown. Using previously published preplate technique, two distinct populations derived cells from were isolated: 1) rapidly adhering cell population (RACs), non-myogenic, Pax7- expresses mesenchymal stem (MSC) marker PDGFRα, hence non-myogenic MSCs (nmMSCs); 2) slowly (SACs) Pax7+ highly myogenic, myogenic progenitor (MPCs). In this dissertation, role nmMSCs histopathogenesis dystrophin/utrophin double knock out (dKO) mice, an animal model DMD, was investigated. become activated progression dKO displaying increased proliferation adipogenic, osteogenic, fibrogenic potentials compared to age-matched WT counterparts. dKO-nmMSCs also significantly reduced potential dKO-MPCs, effect, at least partially, mediated secreted frizzled-related protein 1 (sFRP1) released dKO-nmMSCs. These results suggest that are likely source involved deposition non-muscle muscles activation exacerbates wasting degeneration limiting MPCs. Interestingly, appear play important regeneration after acute injury normal muscle. isolated cardiotoxin injured enhanced MPCs co-cultivation, suggesting may facilitate repair micro-environment plays major fate nMMSCs. Overall, data dissertation proposes therapeutic strategy targeting could represent novel treatment DMD.