Adipose-derived Stem Cells Counteract Urethral Stricture Formation in Rats

Abstract

BackgroundA medical treatment for urethral stricture (US) is not yet available. ObjectiveTo evaluate if local injection of human adipose tissue-derived stem cells (hADSC) prevents urethral fibrosis in a rat model of US. Design, setting, and participantsMale rats were divided into three groups: sham, US, and hADSC (n=12 each). Sham rats received a vehicle injection in the urethral wall. US and hADSCs were incised and injected with the fibrosis-inducer transforming growth factor-β1 in the urethral wall. InterventionOne day later, hADSCs were injected in the urethral wall of hADSC rats whereas sham and US rats were injected with the vehicle. After 4 wk, the rats underwent cystometries and tissues were then harvested for functional and molecular analyses. Outcome measurements and statistical analysisCystometry, microultrasound, histochemistry, organ bath studies, reverse transcription polymerase chain reaction, and western blot. Results and limitationsUS rats exhibited 49–51% shorter micturition intervals, 35–51% smaller micturition volumes and bladder capacity, 33–62% higher threshold pressures and flow pressures, and 35–37% lower bladder filling compliance compared with hADSC-treated rats and sham rats (p<0.05). By ultrasound, US rats had hyperechogenic and thick urethral walls with narrowed lumen compared with sham rats, whereas hADSC rats displayed less extensive urethral changes. Isolated detrusor from US rats exhibited 34–55% smaller contractions than detrusor from sham rats (p<0.05). Corresponding values were 11–35% for isolated detrusors from hADSC rats. Collagen and elastin protein expression were increased in the penile urethras of US rats compared with sham and hADSC groups (p<0.05). Endothelial and inducible nitric oxide synthase expressions were higher (p<0.05) in the hADSC group. Compared with US rats, hADSC rats demonstrated decreased expression of several fibrosis-related genes. Administration of hADSCs was performed at an early stage of US development, which we consider a limitation of the study. ConclusionsLocal injection of hADSCs prevents stricture formation and urodynamic complications in a new rat model for US. Patient summaryStem cell therapy is effective for preventing urethral stricture in an experimental setting.