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

  • Ahmad O. Khalifa
  • Michael Kavran
  • Amr Mahran
  • Ilaha Isali
  • Juliana Woda
  • Chris A. Flask
  • Marc S. Penn
  • Adonis K. HijazEmail author
Original Article


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).


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.


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.


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.


Urinary incontinence Parturition Chemokine CXCL12 Plasmids 



CXC motif chemokine 12




institutional animal care and use committee


interquartile range


leak point pressure


mesenchymal stem cells


phosphate-buffered saline


plasmid of SDF-1


stromal-derived factor-1


skeletal muscle precursor cell


stress urinary incontinence


vaginal distention



Juventus Therapeutics, Inc. provided the pSDF-1 for the experiments.

Preliminary data of part of this work were presented as a moderated poster at the American Urological Association meeting, San Diego, CA, 2016. (Reference: Khalifa A, Mahran A, Kavran M, Woda J, Penn M, Hijaz A (2016) MP65-01 stromal cell derived factor-1 accelerates recovery of continence in rat model of vaginal distension injury. J Urol 195 (4):e864. doi:

Compliance with ethical standards

Conflicts of interest

Ahmad O. Khalifa: no conflict of interest; Michael Kavran: no conflict of interest; Amr Mahran: no conflict of interest; Ilaha Isali: no conflict of interest; Juliana Woda: former commercial developer of SDF-1 plasmid technology at Juventas Therapeutics; Chris A. Flask: no conflict of interest; Marc S. Penn: no conflict of interest; Adonis Hijaz: speaker for Astellas Pharma.


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Copyright information

© The International Urogynecological Association 2019

Authors and Affiliations

  • Ahmad O. Khalifa
    • 1
    • 2
  • Michael Kavran
    • 1
  • Amr Mahran
    • 1
  • Ilaha Isali
    • 1
  • Juliana Woda
    • 3
  • Chris A. Flask
    • 4
    • 5
    • 6
  • Marc S. Penn
    • 7
  • Adonis K. Hijaz
    • 1
    Email author
  1. 1.Department of Urology, University Hospitals Cleveland Medical CenterCase Western Reserve UniversityClevelandUSA
  2. 2.Department of UrologyMenoufia UniversityShibin El KomEgypt
  3. 3.Juventus TherapeuticsClevelandUSA
  4. 4.Departments of RadiologyCase Western Reserve UniversityClevelandUSA
  5. 5.Departments of Biomedical EngineeringCase Western Reserve UniversityClevelandUSA
  6. 6.Departments of PediatricsCase Western Reserve UniversityClevelandUSA
  7. 7.Summa Health Heart and Vascular InstituteAkronUSA

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