Organization and function of the vascular network and its relation with satellite cells in normal and pathological muscle

Abstract

During muscle regeneration, myogenic precursor cells (MPCs) interact with neighbouring cells, including endothelial cells (ECs). Previous studies showed that specific interactions take place between vessel cells and MPCs. However, little is known about their impact on MPC fate and the underlying molecular mechanisms in normal and pathological muscle. We demonstrated in vitro a functional interplay between ECs and MPCs as: – both cell type attract each other in migration assay, suggesting the secretion of specific attractive factors; – ECs strongly stimulate MPC differentiation; – MPCs promote angiogenesis, i.e. differentiation of ECs vessel-like structures. These results were confirmed in vivo, in which MPCs specifically promote the formation of functional vessels in a dose-dependent way. These results show that myogenesis and angiogenesis take place together. Several molecular candidates regulating angiogenesis/myogenesis coupling, including transcriptomic analysis of ECs and MPCs sorted at different time points during muscle regeneration, are under investigation in functional assays. Collectively our results show that specific interactions between MPCs and ECs couple myogenesis and angiogenesis during muscle regeneration. These interactions may be altered in degenerative myopathies, where we already demonstrated strong perturbations of the vascular network associated with functional alteration (weaker muscle perfusion).