CD73 overexpression in ADSCs accelerates bladder repair by regulating the NFκB/NLRP3/caspase-1 signaling axis in neurogenic bladder rats.

Abstract

Neurogenic bladder (NB) is a disabling condition lacking effective therapies. This study investigated whether CD73-expressing adipose-derived stem cells (ADSCs) promote bladder repair in a rat model of NB and explored the underlying mechanisms. ADSCs were sorted into CD73⁺ and CD73⁻ populations, and CD73⁺ cells were further modified to generate CD73⁺^/ev ADSCs and CD73-overexpressing CD73⁺^/⁺ADSCs, while CD73 inhibition was achieved using APCP. Conditioned media were applied to rat bladder smooth muscle cells in vitro, and ADSCs were injected into the bladder wall of rats subjected to bilateral pelvic nerve crush. Four weeks after treatment, bladder function, histology, and molecular markers were evaluated. CD73 overexpression enhanced VEGF and SDF-1 expression, promoted cell proliferation, and reduced inflammatory cytokines, whereas APCP suppressed VEGF. In vivo, CD73⁺^/⁺ADSCs improved cystometric parameters, regenerated bladder tissue, reduced pyroptosis, and activated the PI3K/AKT/mTOR pathway, while suppressing NF-κB/NLRP3/caspase-1 signaling. CD73 expression and VEGF progressively declined in untreated NB rats but were restored by CD73⁺^/⁺ADSCs. These findings indicate that CD73 enhances ADSC-mediated bladder repair through dual pro-regenerative and anti-inflammatory actions, suggesting a promising therapeutic strategy for NB.