Bone marrow mesenchymal stem cells reduce ureteral stricture formation in a rat model via the paracrine effect of extracellular vesicles

Abstract With no effective therapy to prevent or treat ureteral stricture ( US ), a multifactorial fibrotic disease after iatrogenic injury of the ureter, the need for new therapies is urgent. Mesenchymal stem cells ( MSC s) have been widely studied for treating tissue defects and excessive fibrosis, and recent studies established that one of the main therapeutic vectors of MSC s is comprised in their secretome and represented by extracellular vesicles ( EV s). Thus, we have determined to explore the specific role of MSC s‐derived EV s ( MSC ‐ EV s) treatment in a pre‐clinical model of US . The results firstly showed that either a bolus dose of MSC s or a bolus dose of MSC ‐ EV s (administration via renal‐arterial) significantly ameliorated ureteral fibrosis and recuperated ureter morphological development in a US rat model. We confirmed our observations through MSC s or MSC ‐ EV s treatment alleviated hydronephrosis, less renal dysfunction and blunted transforming growth factor‐β1 induced fibration. Due to MSC ‐ EV s are the equivalent dose of MSC s, and similar curative effects of transplantation of MSC s and MSC ‐ EV s were observed, we speculated the curative effect of MSC s in treating US might on account of the release of EV s through paracrine mechanisms. Our study demonstrated an innovative strategy to counteract ureteral stricture formation in a rat model of US .