ИСТИНА

Mesenchymal stem/stromal cells (MSC) are able to regulate tissue repair after injury including the prevention of excessive fibrosis. Extracellular vesicles (EV-MSC) were shown to mediate most of MSC effects and could be involved in their antifibrotic aсtivity. However, the mechanisms of these effects, particularly the role of micro/lncRNA (miR/lncRNA) within EV-MSC, are poorly understood. Human adipose-derived MSC were used to analyze the content of EV-MSC. Using the TargetScan7.2, HMDD, miR2Disease, miRwayDB databases and LncRNADisease v2.0 database, miR and lncRNA associated with the development of fibrosis and their representation in EV-MSC were analyzed. Clustering was performed using the David database. 372 unique miR and 20 genes were associated with TGF-β, of which 24 miR were reliably represented in EV-MSC; 368 unique miR and 22 genes with actin, 23 in EV-MSC; 21 miR and 1 gene with fibrosis; 5 miR and 1 gene with collagen. 73 lncRNA with a 2-fold increase regarding to housekeeping genes RPL13A, GAPDH, B2M, PPIA were selected. Among them at least 3 lncRNA associated with the development of fibrosis by interacting with miR AL139130.1 (miR-9-1), MEG3 (miR-127, miR-136), CARMN (miR-143, miR-145) were identified. Our data indicates the possible impact of miR/lncRNA in antifibrotic activity of EV-MSC. Further study will reveal key noncodingRNA contributors to EV-MSC antifibrotic effects and enable the development of drugs and biomaterials based on miR/lncRNA within EV-MSC that could be promising for regenerative medicine and antifibrotic therapy. The reported study was funded by RFBR according to the research project № 18-015-00525.