Effects of Small Extracellular Vesicles Derived From Mesenchymal Stromal Cells on Acute Kidney Injury: A Rat Ischemia-Reperfusion Model

Extracellular vesicles (EVs) are membrane-bound vesicles, containing nucleic acids, proteins, lipids, amino acids, and metabolites, used for intercellular communication. Several studies indicate that treatment with EVs derived from mesenchymal stromal cells (MSCs) has beneficial effects in acute kidney injury (AKI). MSCs derived from human Wharton's jelly are relatively non-immunogenic with no MHC class II expression and can serve as a viable source for treating human diseases. The aim of this study was to evaluate the effect of EVs derived from human cord tissue-derived MSCs on ischemic/reperfusion (I/R)-induced AKI. A rat I/R-induced AKI model was used, and a total of 33 rats were used in the study. Rats underwent unilateral nephrectomies with simultaneous clamping of the contralateral kidney for 60 minutes, followed by reperfusion. The treatment group received human MSC-derived small EVs, from a single donor, or placebo, and after 48 hours, the rats were sacrificed. Blood was used to evaluate renal function and the inflammatory cascade. Kidneys were taken for histopathologic and inflammation examinations. The EV-treated group significantly improved their renal function compared to the placebo group. Mean creatinine was 1.0 mg/dL in the EV-treated group versus 5.4 mg/dL in the placebo, p=0.005. With respect to the intrarenal inflammatory response, the EV-treated group significantly increased its anti-inflammatory cytokine interleukin-10 levels and attenuated the complement activation compared to the placebo. Perinatal tissue-derived EVs are potentially beneficial for clinical use since they can overcome many safety concerns related to stem cell use. Further clinical trials are needed to better assess these EVs.