Abstract
Mesenchymal stem/stromal cells (MSCs) are the most utilized cell type for cellular therapy, partly due to their important proliferative potential and ability to differentiate into various cell types. MSCs produce large amounts of extracellular vesicles (EVs), which carry genetic and protein cargo to mediate MSC paracrine function. Recently, MSC-derived EVs have been successfully used in several preclinical models of chronic kidney disease. However, uncertainty remains regarding EV fate, safety, and long-term effects, which might impose important limitations on their path to clinical translation. This review discusses the therapeutic application of MSC-derived EV therapy for renal disease, with particular emphasis on potential mechanisms of kidney repair and major translational barriers. Emerging evidence indicates that the cargo of MSC-derived EVs is capable of modulating several pathways responsible for renal injury, including inflammation, oxidative stress, apoptosis, fibrosis, and microvascular remodeling. EV-induced modulation of these pathways has been associated with important renoprotective effects in experimental studies. However, scarce clinical data are available, and several challenges need to be addressed as we move toward clinical translation, including standardization of methods for EV isolation and characterization, EV fate, duration of EV effects, and effects of cardiovascular risk factors. MSC-derived EVs have the potential to preserve renal structure and function, but further experimental and clinical evidence is needed to confirm their protective effects in patients with chronic kidney disease.