Their role in vivo may be related to cell-to-cell communication

and to proteins and RNAs exchange among cells both locally and at distance[44]. The buy Tofacitinib discovery of mRNAs and miRNAs in exosomes foreshadows an important new direction for their application as delivery vehicles for therapeutics. In vitro and in vivo experiments have demonstrated that MVs released by BM MSC activate proliferation in tubular epithelial cells and restore renal function after glycerol-induced injury. This regenerative activity is related to the presence of specific mRNAs that encode proteins responsible for controlling proliferation, transcription and immune response[45]. MVs intravenously injected in rat immediately after inducing ischemic- reperfusion injury reduced apoptosis and increased cellular proliferation

of tubular cells. Inactivation of MV cargos with RNAase determined the lack of protective effects[46]. Multiple injections of MVs in cisplatin- induced lethal model of AKI SCID mice reduced mortality and produced a normal histological phenotype with normal renal function in surviving animals[47]. The analysis of bio-distribution and renal localization of MVs has demonstrated that MVs accumulated specifically in the kidneys of the mice with AKI compared with the healthy controls. Two different protocols have been used to dye MVs: the near infra-red dye was added to cell culture medium or MVs were stained after purification. Interestingly, the signal generated by the labeled MVs produced by cells was more specific for the injured tissue than those from directly labeled MVs[48]. A therapeutic effect in renal ischemia-reperfusion injury has been shown also by MVs derived from human Wharton-Jelly MSCs. Indeed, a single administration of these MVs in rat immediately after inducing AKI reduced inflammation, and, as long-term outcome, improved

renal function and decreased fibrosis[49]. The mechanism of Carfilzomib action of Wharton-Jelly MSC derived MVs has not been completely elucidated, but it has been observed that these MVs mitigated the oxidative stress and declined NOX2 expression and reactive oxygen species generation[50]. A further source of MVs with renoprotective activity is the kidney mesenchymal stem cells (KMSC). These microparticles were isolated from the supernatants of KMSC cultured in anoxic conditions in serum-deprived media for 24 h; when injected in mice with acute renal ischemia, they significantly improved renal function, favoring endothelial cells proliferation and ameliorating peritubular microvascular rarefaction[51].