Stem Cell-Based Strategies for Fibrotic and Neurogenic Bladder Disorders: Current Evidence, Translational Challenges, and Future Directions

Progressive bladder fibrosis and impaired detrusor function represent converging pathological endpoints across diverse bladder disorders, including bladder outlet obstruction (BOO) associated with benign prostatic hyperplasia, spinal cord injury (SCI)-induced neurogenic bladder, radiation cystitis, and interstitial cystitis/bladder pain syndrome. Conventional therapies primarily manage symptoms and rarely reverse established fibrosis or restore durable bladder homeostasis. Mesenchymal stem/stromal cells (MSCs) have attracted considerable interest as therapeutic agents owing to their antifibrotic, immunomodulatory, angiogenic, and trophic paracrine activities. This review synthesises six key studies from our group and places them within the broader international literature on bladder regenerative medicine: (i) feasibility of superparamagnetic iron oxide (SPIO)-based molecular MRI tracking of transplanted human MSCs (hMSCs) in the bladder; (ii) SPIO-hMSC therapy for BOO-associated fibrosis with concurrent MRI monitoring; (iii) hepatocyte growth factor (HGF)-overexpressing engineered hMSC (B10.HGF) therapy in BOO; (iv) hMSC transplantation into the SCI-injured bladder wall monitored by MRI; (v) systematic review and meta-analysis of stem cell therapy effects on urodynamic outcomes in SCI models; and (vi) HGF-overexpressing hMSC therapy for BOO-induced underactive bladder. These six key studies are contextualised within the broader literature addressing cell sources, biomaterial-assisted delivery platforms, mechanistic pathways, emerging clinical evidence, and the evolving regulatory landscape for cell-based advanced therapy medicinal products. Key translational challenges include product standardisation, long-term durability, and mechanism-linked potency assay development.