Bladder urothelial injury is a key pathological process in interstitial cystitis/bladder pain syndrome (IC/BPS). Although several intravesical instillation therapies have been developed to promote urothelial repair, their long-term efficacy remains limited. Therefore, exploring targeted therapies that enhance endogenous bladder regeneration is of great significance. Proliferative bladder organoids possess multiple proliferation and differentiation potentials, and specific cell populations and their secreted factors can promote urothelial self-repair. However, their therapeutic effect on IC/BPS remains unknown. This study aims to investigate the efficacy of bladder organoid instillation in treating IC/BPS and promoting bladder urothelial repair.

Bladder organoids were constructed from healthy rat bladders and identified through immunofluorescence staining, light microscopy, and transcriptome sequencing. Eighteen six-week-old female SD rats were randomly divided into three groups: control, model (CYP-induced, single intraperitoneal injection of 150 mg/kg), and model + organoid treatment group. After successful modeling, the organoid group received two intravesical instillations, with a three-day interval, and each instillation was retained for one hour. Pain behavior and urinary spot changes were recorded. After the second treatment, bladder tissues were collected for histological analysis to evaluate urothelial repair and inflammatory response.

The proliferative bladder organoids exhibited higher expression of proliferation- and stemness-related genes and showed enhanced differentiation potential. Organoid intravesical instillation in CYP-induced bladder injury rats reduced pain behavior and urinary urgency frequency. Additionally, it inhibited bladder urothelial inflammation and promoted epithelial self-repair.

The study demonstrates that bladder organoids not only survive and integrate into the injured bladder urothelium but also actively contribute to its repair. The reduction in inflammatory markers and improvement in bladder epithelial integrity suggest that bladder organoids can modulate the local microenvironment to support endogenous healing processes. This highlights their potential as a viable cell-based therapy for IC/BPS, offering an alternative to conventional intravesical treatments that lack sustained efficacy. Further research is needed to optimize organoid delivery and assess long-term therapeutic outcomes in preclinical and clinical settings.

Proliferative bladder organoids exhibit superior proliferation and differentiation potential and possess better homology with the bladder. Intravesical instillation of proliferative bladder organoids represents a promising endogenous therapeutic approach for bladder repair in IC/BPS.