Mesenchymal stem Cells and Extracellular Vesicles in Bladder Dysfunction: Mechanisms and Translational Perspectives

Bladder dysfunction comprises diverse lower urinary tract disorders lacking treatments that restore tissue integrity and neural control. While mesenchymal stem cells (MSCs) show promise in regenerative urology, their benefits primarily stem from paracrine mechanisms. Consequently, MSC-derived extracellular vesicles (MSC-EVs) have emerged as superior cell-free alternatives, recapitulating the parent cells' regenerative potential with enhanced biosafety, stability, and controllability.This review summarizes advances in MSC- and MSC-EV-based therapies for bladder conditions, including neurogenic, diabetic, overactive/underactive bladder, outlet obstruction, and interstitial cystitis. Mechanistically, these therapies exert multi-target effects: modulating immunity, suppressing fibrosis (via TGF-β inhibition), attenuating inflammation (via NF-κB/NLRP3), promoting angiogenesis, and enhancing neuroregeneration. MSC-EVs drive these processes by precisely transferring bioactive microRNAs and proteins.We propose a paradigm shift from conventional cell therapies to MSC-EV-centric, cell-free strategies, which overcome traditional transplantation limitations like low engraftment and immunogenicity. While early data confirm feasibility and safety, challenges in standardizing EV isolation, dosing, and long-term efficacy remain. Ultimately, this review establishes MSC-EVs as a next-generation therapeutic framework, guiding future clinical translation in regenerative urology.