The preventative effect of bone marrow-derived mesenchymal stem cell exosomes on urethral stricture in rats

Abstract

Urethral stricture (US) is a major challenge in urology and there is an urgent need for effective therapies for its treatment. Exosomes derived from bone marrow mesenchymal stem cells (BMSC-Exos) have been shown to be effective in preventing scar and fibrosis formation after tissue injury. However, the potential utility of BMSCs-Exos in the prevention of US remains unknown. We hypothesized that local administration of BMSC-Exos may influence urethral healing and scar formation in a rat model of US. A previously established model of rat US was used in this study. Sprague Dawley rats were randomly assigned into sham, US, and US + BMSC-Exos groups. Microultrasound assessment, histopathology, immunohistochemistry, and gene expression analysis were performed at four weeks post-surgery. US rats exhibited thick urethral walls with a narrowed lumen, when compared with sham rats. However, these changes were suppressed in the US + BMSC-Exos group. The preventative effects of BMSC-Exos on US formation were also apparent histologically. US + BMSC-Exos rats demonstrated decreased expression of several fibrosis-related genes in urethral tissues, including Col I, fibronectin, and elastin, when compared with US rats. BMSC-Exos treatment also led to an increase in the expression of angiogenesis-related genes in these tissues, including VEGF, eNOS, and bFGF. Our findings therefore demonstrate that the local administration of BMSC-Exos prevents urethral stricture formation by regulating fibrosis and angiogenesis. These findings provide a basis for an innovative strategy involving the clinical application of exosomes to counteract US formation.