Therapeutic Potential of Mesenchymal Stromal Cell-derived Small Extracellular Vesicles

Small extracellular vesicles (sEVs) are biological nanoparticles with sizes below 200 nm that are released by virtually all cells and are detected in all body fluids. Assembled in cell type specific manners, at least a proportion of the sEVs can transmit complex information from the sending to specifically selected target cells. Depending on their origin, signalling sEVs can modulate physiological and pathophysiological processes. sEVs released from mesenchymal stem/ stromal cells (MSCs) for example mediate therapeutic activities in an increasing number of different diseases. Although their concrete mechanisms of action (MoA) as well as their side(s) of action (SoA) have not been sufficiently dissected, yet, MSC-sEVs apparently act in multimodal manners. Evidence has been provided that as part of their therapeutic activities MSC-sEV preparations can modulate pro-inflammatory into regulatory/tolerogenic immune responses, promote angiogenic and pro-regenerative processes and act anti-apoptotically as well as energy restoring. Here, we summarize the history behind the discovery of the therapeutic activities of MSC-sEVs, some of their therapeutic application fields, and challenges connected with their effective translation into the clinics.