Analysis of renoprotective effects of inoculation of extracellular vesicles derived from mesenchymal stem cells in experimental chronic kidney disease

Abstract

Chronic Kidney Disease (CKD) is characterized by the progressive and irreversible loss ofkidney functions. Currently, the therapeutic arsenal used to control CKD is limited toapplication of RAAS inhibitor drugs, diuretics and immunosuppressive drugs, eventuallyrelated to side effects. Recent data in the literature have shown that the application ofmesenchymal stem cells (MSC) in the kidney tissue of animals submitted toCKD experiments promoted renoprotective effects in containing disease progressionthrough immunomodulatory and anti-fibrotic pathways. Most of these works have shownthat the positive effects obtained with the inoculation of MSC do not derive from the in situ differentiation of thethe same, but of cell signaling mechanisms that MSC would be able to triggerthrough the secretion of factors in the inflammatory microenvironment, in addition to releasing vesiclesextracellular (EV) that would act as cell-cell communication, promoting the modulation ofinflammation in the tissue, reducing the stimulus to fibrogenesis. Due to this potential effectimmunomodulator of MSC-derived EV, these have become one of the most explored focusesin the study of therapy with cellular by-products applied to chronic-degenerative diseases. WithBased on the above, the objective of the present study is to evaluate the renoprotective effects of inoculationsubcapsular of extracellular vesicles derived from MSC in rats submitted to the5/6 renal ablation (5/6Nx). As well as verifying if their application promotes effectsrenoprotectants equivalent to those obtained with the whole mesenchymal stem cell adipose tissue, delaying thedevelopment of CKD in this model, in addition to analyzing the therapeutic effects of the application ofMSC-derived EV in association with pharmacological treatment with a BRAT1 blocker, making a parallel with the conditions observed in clinical practice in conservative treatmentof the DRC. (AU)