Renoprotective effects of extracellular vesicles derived from mesenchymal stem cells, in an advanced model of Chronic Kidney Disease

Abstract

Chronic kidney disease (CKD), characterized by the progressive and irreversible loss of kidney functions, is currently considered an importat global health issue, due to both its increasing incidence and its high morbidity and mortality.The therapeutic arsenal employed to the conservative management of human CKD is mostly based on the pharmacological blockade of the renin-angiotensin-aldosterone system (RAAS), associated or not to diuretics and immunosuppressants. However, even these combined strategies are ineffective to contain the progression of CKD to the end-stage renal failure. The lack of a specific drug, effective to prevent or avoid the need for renal replacement therapy, motivates physicians and life sciences researchers to search for alternative treatments for controlling CKD. In this context, the current literature have shown cell therapy, with mesenchymal stem cells (mSC) to promote important renoprotective effects in experimental nephropathy, when associated to RAAS blockers. Further studies suggest that such beneficial effects may come from cell signaling mechanisms mSCs would be able to trigger through the secretion of extracellular vesicles (EV) containing cytokines, growth factors and RNA fragments in the inflammation microenvironment, when inoculated into the damaged tissue. Based on the above, the aim of the present study is to evaluate the renoprotective effects of subcapsular and intravenous inoculation of EV or mSC, associated to the pharmacological RAAS blockade, in rats submitted to an advanced CKD model. (AU)