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

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

International Urogynecology Journal, 2020, Vol.31 (1), p.107-115 [Periódico revisado por pares]

Cham: Springer International Publishing

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  • Título:
    Stromal derived factor-1 plasmid as a novel injection for treatment of stress urinary incontinence in a rat model
  • Autor: Khalifa, Ahmad O. ; Kavran, Michael ; Mahran, Amr ; Isali, Ilaha ; Woda, Juliana ; Flask, Chris A. ; Penn, Marc S. ; Hijaz, Adonis K.
  • Assuntos: Animals ; Chemokine CXCL12 - genetics ; Disease Models, Animal ; Genetic Therapy - methods ; Gynecology ; Injections ; Medicine ; Medicine & Public Health ; Original Article ; Plasmids ; Puerperal Disorders - prevention & control ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Stem cells ; Tissue engineering ; Urinary incontinence ; Urinary Incontinence, Stress - prevention & control ; Urology
  • É parte de: International Urogynecology Journal, 2020, Vol.31 (1), p.107-115
  • Notas: ObjectType-Article-2
    SourceType-Scholarly Journals-1
    ObjectType-Undefined-1
    ObjectType-Feature-3
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  • Descrição: 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 cmH 2 O versus 13.99 cmH 2 O, p < 0.001). Functional improvement persisted until the 14th day (30.51 cmH 2 O versus 24.11 cmH 2 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.
  • Editor: Cham: Springer International Publishing
  • Idioma: Inglês
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  • Realização: ABCD-USP USP   Logos de Redes Sociais: Freepik

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