Basking in their niche: stem cells with myogenic potential as a target to combat cachexia

Skeletal muscle contains several myogenic populations: satellite cells, muscle derived stem cells, PW1+ stem cells, mesoangioblasts / pericytes, fibroadipogenic progenitor cells, and hematopoietic stem cells. In response to muscle damage in cachexia, these myogenic populations proliferate, but fail to fuse into myofibers. Substantial evidence points to pro-inflammatory cytokines and other anti-myogenic factors, which apparently are responsible for this paradoxical increase in the muscle stem-cell pool in wasting muscle. Therapeutic efforts are currently aimed at counteracting myofiber catabolism and atrophy; nonetheless, functional myogenic cells could be an additional therapeutic targets. As in dystrophic muscles, myogenic cells can sustain muscle homeostasis for a long time, even in the presence of overt muscle damage and wasting. Many tools are already available to stimulate their differentiation, from exercise to the pharmacological removal of inhibitory signals blocking this very differentiation. However, an extended characterization of the various myogenic stem-cell populations, in search of the one resistant to cachectic factors, has not been performed to date. The identification of either an engineered or an endogenous myogenic cell type able to differentiate or fuse to cachectic myofibers in the presence of a non-permissive milieu would represent a revolutionary approach to counteract cachexia.