Extracellular Microvesicles (MV's) Isolated from 5-Azacytidine-and-Resveratrol-Treated Cells Improve Viability and Ameliorate Endoplasmic Reticulum Stress in Metabolic Syndrome Derived Mesenchymal Stem Cells.

Extracellular vesicles (EVs), a spherical membrane fragments including exosomes, are released from several cell types, including mesenchymal stromal cells (MSCs), constitutively or under stimulation. As MVs cargo include DNA, RNA, miRNA, lipids and proteins their have gain special attention in the field of regenerative medicine. Depending on the type of transferred molecules, MVs may exert wide range of biological effects in recipient cells including pro-inflammatory and anti-apoptotic action. In presented paper, we isolated MVs form adipose derived mesenchymal stem cells (ASC) which underwent stimulation with 5-azacytydine and resveratrol (AZA/RES) in order to improve their therapeutic potential. Then, isolated MVs were applied to ASC with impaired cytophysiological properties, isolated from equine metabolic syndrome diagnosed animals. Using RT-PCR, immunofluorescence, ELISA, confocal microscopy and western blot, we have evaluated the effects of MVs on recipient cells. We have found, that MVs derived from AZA/RES treated ASC ameliorates apoptosis, senescence and endoplasmic reticulum (ER) stress in deteriorated cells, restoring their proper functions. The work indicates, that cells treated with AZA/RES through their paracrine action can rejuvenate recipient cells. However, further research needs to be performed in order to fully understand the molecular mechanisms of these bioactive factors action. Graphical Abstract Graphical abstract of presented study.