Effects of mesenchymal stem cells and heparan sulfate mimetics on urethral function and vaginal wall biomechanics in a simulated rat childbirth injury model.

INTRODUCTION AND HYPOTHESIS: New treatments are needed for pelvic floor disorders. ReGeneraTing Agent® (RGTA®) is a promising regenerative therapy. Therefore, the objective of this study was to compare regenerative abilities of mesenchymal stem cells (MSCs) and RGTA® on regeneration after simulated childbirth injury in rats. METHODS: Rats underwent pudendal nerve crush and vaginal distension (PNC+VD) or sham injury. Rats that underwent PNC+VD were treated intravenously with vehicle, MSCs or RGTA® 1 h, 7 days, and 14 days after surgery. Sham rats received 1 ml vehicle at all time points. After 21 days, urethral function and pudendal nerve function were tested. Vaginal tissues were harvested for biomechanical testing and histology. Biaxial testing was performed to measure tissue stiffness. RESULTS: PNC+VD decreased urethral and pudendal nerve function compared with sham. Vaginal wall stiffness was significantly decreased in longitudinal and transverse tissue axes after PNC+VD compared with sham. MSC or RGTA® did not restore urethral or pudendal nerve function. However, MSC treatment resolved loss in vaginal wall stiffness in both tissue axes and improved collagen content within the vaginal wall. RGTA® treatment increased vaginal wall anisotropy by increasing relative stiffness in the longitudinal direction. PNC+VD (with vehicle or MSCs) enhanced elastogenesis, which was not observed after RGTA® treatment. CONCLUSIONS: Treatment with MSCs facilitated recovery of vaginal wall biomechanical properties and connective tissue composition after PNC+VD, whereas treatment with RGTA® resulted in anisotropic biomechanical changes. This indicates that MSCs and RGTA® promote different aspects of vaginal tissue regeneration after simulated childbirth injury.

Multiple doses of stem cells maintain urethral function in a model of neuromuscular injury resulting in stress urinary incontinence.

Stress urinary incontinence (SUI) is more prevalent among women who deliver vaginally than women who have had a cesarean section, suggesting that tissue repair after vaginal delivery is insufficient. A single dose of mesenchymal stem cells (MSCs) has been shown to partially restore urethral function in a model of SUI. The aim of the present study was to determine if increasing the number of doses of MSCs improves urethral and pudendal nerve function and anatomy. We hypothesized that increasing the number of MSC doses would accelerate recovery from SUI compared with vehicle treatment. Rats underwent pudendal nerve crush and vaginal distension or a sham injury and were treated intravenously with vehicle or one, two, or three doses of 2 × 106 MSCs at 1 h, 7 days, and 14 days after injury. Urethral leak point pressure testing with simultaneous external urethral sphincter electromyography and pudendal nerve electroneurography were performed 21 days after injury, and the urethrovaginal complex and pudendal nerve were harvested for semiquantitative morphometry of the external urethral sphincter, urethral elastin, and pudendal nerve. Two and three doses of MSCs significantly improved peak pressure; however, a single dose of MSCs did not. Single, as well as repeated, MSC doses improved urethral integrity by restoring urethral connective tissue composition and neuromuscular structures. MSC treatment improved elastogenesis, prevented disruption of the external urethral sphincter, and enhanced pudendal nerve morphology. These results suggest that MSC therapy for postpartum incontinence and SUI can be enhanced with multiple doses.

Transurethral versus suprapubic catheterization to test urethral function in rats.

Transurethral and suprapubic catheterization have both been used to test urethral function in rats; however, it is unknown whether these methods affect urethral function or if the order of catheterization affects the results. The aim of this cross-over designed experiment was to compare the effects of catheterization methods and order on leak point pressure (LPP) testing. LPP and simultaneous external urethral sphincter electromyography (EUS EMG) were recorded in anesthetized female virgin Sprague-Dawley rats in a cross-over design to test the effects of transurethral and suprapubic catheterization. There was no significant difference in peak bladder pressure during LPP testing whether measured with a transurethral or suprapubic catheter. There was no significant difference in peak bladder pressure between the first and second catheter insertions. However, peak EMG firing rate, as well as peak EMG amplitude and EMG amplitude difference between peak and baseline were significantly higher after the first catheter insertion compared to the second insertion, regardless of the catheter method. Our results suggest that route of catheterization does not alter urethral function, e.g. create a functional partial outlet obstruction. Either catheterization method could be used for LPP and/or EUS EMG testing in rats.

The Quality of Health Information Available on the Internet for Patients With Pelvic Organ Prolapse.

OBJECTIVE: This study aimed to assess the quality of Web sites that provide information on pelvic organ prolapse using validated quality measurement tools. METHODS: The Google search engine was used to perform a search of the following 4 terms: "pelvic organ prolapse," "dropped bladder," "cystocele," and "vaginal mesh." The DISCERN appraisal tool and JAMA benchmark criteria were used to determine the quality of health information of each Web site. Cohen κ was performed to determine interrater reliability between reviewers. Kruskal-Wallis and Wilcoxon rank sum tests were used to compare DISCERN scores and JAMA criteria among search terms. RESULTS: Interrater reliability between the two reviewers using DISCERN was κ = 0.71 [95% confidence interval (CI), 0.68-0.74] and using JAMA criteria was κ = 0.98 (95% CI, 0.74-1.0). On the basis of the DISCERN appraisal tool, the search term "vaginal mesh" had significantly lower Web site quality than "pelvic organ prolapse" and "cystocele," respectively [mean difference of DISCERN score, -14.65 (95% CI, -25.50 to 8.50, P < 0.0001) and -12.55 (95% CI, -24.00 to 7.00, P = 0.0007)]. "Dropped bladder" had significantly lower Web site quality compared to "pelvic organ prolapse" and "cystocele," respectively (mean difference of DISCERN score, -9.55 (95% CI, -20.00 to 3.00, P = 0.0098) and -7.80 (95% CI, -18.00 to 1.00, P = 0.0348). Using JAMA criteria, there were no statistically significant differences between Web sites. CONCLUSIONS: Web sites queried under search terms "vaginal mesh" and "dropped bladder" are lower in quality compared with the Web sites found using the search terms "pelvic organ prolapse" and "cystocele."