Mesenchymal Stromal Cell-Derived Extracellular Vesicles: Their Features and Impact on Fibrosis and Myogenesis in Vitro

Extracellular vesicles (EVs) and, particularly, exosomes are becoming a promising material for "cell-free therapy" of many pathologic conditions. In the recent years therapeutic effects of mesenchymal stromal cells (MSCs) have been attributed to their secretory factors, including EVs. In this study we aim to investigate how EVs produced by MSCs of different tissue origin can influence myogenesis and fibrosis-the main processes that accompany skeletal muscle regeneration. Bone marrow, adipose tissue, intact muscle, and injured muscle-derived rat MSCs were obtained and cultured according to standard protocols. EVs were obtained by ultracentrifugation from the MSC-conditioned medium of cell passages 2 and 3. The effects of EVs were estimated on the in vitro models of myogenesis and fibrosis. Samples of isolated EVs contained nano-sized vesicles that carried some exosomal markers. Promyogenic microRNA were found in EVs from bone marrow and muscle MSCs. We found that MSC-derived EVs from all sources significantly increased the number of newly formed myotubes in myoblast culture in vitro and also reduced the number and size of fibrotic nodules in muscle fibroblast culture in vitro. Our results suggest that MSC-derived EVs indeed possess antifibrotic and promyogenic potentials. However, the role of microRNA in these processes is yet to be determined, and the effect of EVs on skeletal muscle regeneration is yet to be tested in vivo.