Mesenchymal stem cell-derived extracellular vesicles for kidney repair: Current status and looming challenges

Novel therapies are urgently needed to address the rising incidence and prevalence of acute kidney injury (AKI) and chronic kidney disease (CKD). Mesenchymal stem/stromal cells (MSCs) have shown promising results in experimental AKI and CKD, and have been used in the clinic for more than a decade with an excellent safety profile. The regenerative effects of MSCs do not rely on their differentiation and ability to replace damaged tissues, but are primarily mediated by the paracrine release of factors, including extracellular vesicles (EVs), composed of microvesicles and exosomes. MSC-derived EVs contain genetic and protein material that upon transferring to recipient cells can activate several repair mechanisms to ameliorate renal injury. Recent studies have shown that MSC-derived EV therapy improved renal outcomes in several animal models of AKI and CKD, including ischemia-reperfusion injury, drug/toxin-induced nephropathy, renovascular disease, ureteral obstruction, and subtotal nephrectomy. However, data about the renoprotective effects of EV therapy in patients with renal failure are scarce. This review summarizes current knowledge of MSC-derived EV therapy in experimental AKI and CKD, and discusses the challenges that need to be addressed in order to consider MSC-derived EVs as a realistic clinical tool to treat patients with these conditions.