ABSTRACT
Mesenchymal stromal cell (MSCs) represent a class of biologics with the prospects for employment as immunomodulatory, tissue-protective, and regenerative therapeutics. In parallel with cellular therapy, cell-free therapy based on MSC-secreted bioactive factors is being actively developed. MSCs secrete a variety of protein, peptide, RNA, and lipid mediators which can be concentrated, frozen, or even lyophilized without loss of activity, which gives them a certain advantage over cellular products requiring liquid nitrogen storage and infrastructure to revive frozen cells. This review (i) describes currently conducted clinical trials of cell-free products containing MSC secretome; (ii) summarizes main approaches to the generation and characterization of conditioned media concentrates and extracellular vesicle isolates; (iii) analyzes a variety of preclinical studies where effectiveness of secretome products has been shown; and (iv) summarizes current knowledge about secretome bioactive components obtained by analysis of in vivo models testing the therapeutic potential of the MSC secretome.