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21.01.2019 | Original Article

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

verfasst von: Ahmad O. Khalifa, Michael Kavran, Amr Mahran, Ilaha Isali, Juliana Woda, Chris A. Flask, Marc S. Penn, Adonis K. Hijaz

Erschienen in: International Urogynecology Journal

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Abstract

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 cmH2O versus 13.99 cmH2O, p < 0.001). Functional improvement persisted until the 14th day (30.51 cmH2O versus 24.11 cmH2O, 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.
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Metadaten
Titel
Stromal derived factor-1 plasmid as a novel injection for treatment of stress urinary incontinence in a rat model
verfasst von
Ahmad O. Khalifa
Michael Kavran
Amr Mahran
Ilaha Isali
Juliana Woda
Chris A. Flask
Marc S. Penn
Adonis K. Hijaz
Publikationsdatum
21.01.2019
Verlag
Springer International Publishing
Erschienen in
International Urogynecology Journal
Print ISSN: 0937-3462
Elektronische ISSN: 1433-3023
DOI
https://doi.org/10.1007/s00192-019-03867-3

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