Stromal derived factor-1 plasmid as a novel injection for treatment of stress urinary incontinence in a rat model.

INTRODUCTION AND HYPOTHESIS: SDF-1 chemokine enhances tissue regeneration through stem cell chemotaxis, neovascularization and neuronal regeneration. We hypothesized that non-viral delivery of human plasmids that express SDF-1 (pSDF-1) may represent a novel regenerative therapy for stress urinary incontinence (SUI).

METHODS: Seventy-six female rats underwent vaginal distention (VD). They were then divided into four groups according to treatment: pSDF-1 (n = 42), sham (n = 30), PBS (n = 1) and luciferase-tagged pSDF-1 (n = 3). Immediately after VD, the pSDF-1 group underwent immediate periurethral injection of pSDF-1, and the sham group received a vehicle injection followed by leak point pressure (LPP) measurement at the 4th, 7th and 14th days. Urogenital tissues were collected for histology. H&E and trichrome slides were analyzed for vascularity and collagen/muscle components of the sphincter. For the luciferase-tagged pSDF-1 group, bioluminescence scans (BLIs) were obtained on the 3rd, 7th and 14th days following injections. Statistical analysis was conducted using ANOVA with post hoc LSD tests. The Mann-Whitney U test was employed to make pair-wise comparisons between the treated and sham groups. We used IBM SPSS, version 22, for statistical analyses.

RESULTS: BLI showed high expression of luciferase-tagged pSDF-1 in the pelvic area over time. VD resulted in a decline of LPP at the 4th day in both groups. The pSDF1-treated group demonstrated accelerated recovery that was significantly higher than that of the sham-treated group at the 7th day (22.64 cmH2 O versus 13.99 cmH2 O, p < 0.001). Functional improvement persisted until the 14th day (30.51 cmH2 O versus 24.11 cmH2 O, p = 0.067). Vascularity density in the pSDF-1-treated group was higher than in the sham group at the 7th and 14th days (p < 0.05). The muscle density/sphincter area increased significantly from the 4th to 14th day only in the pSDF-1 group.

CONCLUSIONS: Periurethral injection of pSDF-1 after simulated childbirth accelerated the recovery of continence and regeneration of the urethral sphincter in a rat SUI model. This intervention can potentially be translated to the treatment of post-partum urinary incontinence.