The Use of Autologous Skeletal Muscle Derived Cells as a Sling in the Treatment of Induced Stress Urinary Incontinence, An Experimental Study in Dogs

Introduction:This is an experimental pre-clinical study, testing the applicability of autologous skeletal muscle derived cells as a treatment of SUI in canine modelMethods:10 Mongrel dogs included. Skeletal muscle biopsy was harvested in 4. 1 month later, incontinence was induced in 8 dogs through urethrolysis. Muscle biopsy was incubated and expanded for 8 weeks. Muscle derived cells were collected and covered a Polyglycolic acid (PGA) scaffold immersed in culture medium and coated with matrigel to be used as a sling. Placed suburethral in 8 dogs; 4 had cell- seeded and 4 had scaffold only. Urethral pressure (UP) measurement was done at baseline 2 &6 weeks after sling insertion. The urethra was harvested 4 weeks after sling insertion for histopathology.Results:UP shows increase of maximum urethral pressure during static measurement in all dogs with a scaffold inserted. The increase ranged from 5-40 cmH20 Histopathology shows significant periurethral proliferation of skeletal muscles in 4 dogs with cell-seeded scaffold. This was maximum in dogs # 1& 2. This was not the case in the 4 dogs that had sling only.Conclusion: Use of skeletal muscle –seeded PGA scaffold is a practical technique with preserved integrity of histological differentiation in canine model.

The Role of Anterior Bladder Flap Neourethra (ABFN) in Early Urinary Continence after Laparoscopic Radical Prostatectomy The Anterior Bladder Flap Neourethra (ABFN) in RP

Purpose To evaluate the impact of anterior bladder flap neourethra (ABFN) technique on early urinary continence after laparoscopic radical prostatectomy(RP). Materials and Methods Forty patients who underwent laparoscopic RP January 2019 to January 2021 were prospectively randomized into two groups: the ABFN group (n = 20) and the control group (n = 20). We compared continence rates and ICIQ-SF at 1d, 30 d, 90 d and 180 d after catheter removal. In addition, the urethral pressure of two groups, the length and thickness of neourethra in the ABFN group were measured at one week after catheter removal. Results The ABFN group had marked improvement incontinence rates at 1d, 30d and 90d after catheter removal vs the control group, while had the nearly same continence rate at 180 d. ICIQ-SF scores of the ABFN group were lower than the control group. Maximal urethral pressure (MUP), functional urethral length (FUL) and functional urethral area (UFA) for the ABFN group has significantly improvement than the control group. MRI showed that the neourethral length of the ABFN group was 13.7–16.2 mm, the thickness was 3.6–5.2 mm. Conclusions The ABFN technique markedly improved the early continence rate after laparoscopic RP.

The use of autologous skeletal muscle-derived cells as a sling in the treatment of induced stress urinary incontinence, an experimental study

Introduction & hypothesis: This is an experimental pre-clinical study testing for the applicability of autologous skeletal muscle derived cells as a seeded sling for the treatment of Stress urinary incontinence in canine model. Methods: 10 Mongrel dogs: In 4, skeletal muscle biopsy was harvested from Biceps Femoris. 1 month later, incontinence was induced in 8 dogs through surgical disruption of the pubourethral ligaments. Muscle biopsy was incubated in medium and after expansion for 8 weeks, Muscle derived cells were collected. Polyglycolic acid scaffold was immersed in culture medium, coated with matrigel and cells were seeded. The sling was placed suburethral in 8 dogs; 2 of which were cell-seeded and 4 had the scaffold only. Urethral pressure measurement was done at baseline and 2 weeks after insertion of the sling. The urethra with its surrounding was harvested 4 weeks after sling insertion for histopathology. 2 dogs were considered as control, in which no urethrolysis or insertion of slings was carried out. Results: Urethral pressure shows increase of maximum urethral pressure during static measurement in all dogs with a scaffold inserted. The increase ranged from 5-40 centimeter water (Median: 23 cmH20). Histopathology shows significant periurethral proliferation of skeletal muscles in 4 dogs with cell-seeded scaffold, as demonstrated by Desmin. This was maximum in dogs numbers 1and 2. This was not the case in the 4 dogs that had Polyglycolic acid sling only. Conclusion: The use of skeletal muscle-seeded scaffold is a practical technique with preserved integrity of histological differentiation in canine model at short term.

The Mode of Action of Adjustable Transobturator Male System (ATOMS): Intraoperative Urethral Pressure Measurements

(1) Background: The Adjustable Transobturator Male System (ATOMS) device is increasingly used to treat post-prostatectomy incontinence as it enhances residual urinary sphincteric function and allows continence recovery or improvement by dorsal compression of the bulbar urethra through a fixed transobturator mesh passage. The mode of action and the profile of the patients with best results are not totally understood. (2) Methods: Intraoperative urethral pressure measurements at different filling levels of the ATOMS device show increased urethral resistance and enhanced residual sphincteric activity. We evaluated whether the pattern of urethral pressure change secondary to serial progressive intraoperative filling of the cushion can predict postoperative results after ATOMS placement. (3) Results: The regression analysis showed a significant direct relationship between cushion volume and intraurethral pressure (p = 0.000). The median intraurethral pressure at atmospheric pressure was 51 ± 22.7 cm H2O, and at atmospheric pressure plus 4 mL was 80 ± 23.1 cm H2O). Cluster analyses defined a group of patients (n = 6) formed by patients with a distensible urethra and 100% continence after adjustment in contrast to another group (n = 3) with rigid urethras and 33% continence after adjustment. (4) Conclusions: As a part of its continence mechanism, the ATOMS device leads to continence by increasing intraurethral pressure owing to the stretching effect on the urethral wall caused by cushion filling that increases urethral resistance.

Targeted neuromodulation of pelvic floor nerves in aging and multiparous rabbits improves continence

Pelvic floor muscle stretch injury during pregnancy and birth is associated with the incidence of stress urinary incontinence (SUI), a condition that affects 30–60% of the female population and is characterized by involuntary urine leakage during physical activity, further exacerbated by aging. Aging and multiparous rabbits suffer pelvic nerve and muscle damage, resulting in alterations in pelvic floor muscular contraction and low urethral pressure, resembling SUI. However, the extent of nerve injury is not fully understood. Here, we used electron microscopy analysis of pelvic and perineal nerves in multiparous rabbits to describe the extent of stretch nerve injury based on axon count, axon size, myelin-to-axon ratio, and elliptical ratio. Compared to young nulliparous controls, mid-age multiparous animals showed an increase in the density of unmyelinated axons and in myelin thickness in both nerves, albeit more significant in the bulbospongiosus nerve. This revealed a partial but sustained damage to these nerves, and the presence of some regenerated axons. Additionally, we tested whether electrical stimulation of the bulbospongiosus nerve would induce muscle contraction and urethral closure. Using a miniature wireless stimulator implanted on this perineal nerve in young nulliparous and middle age multiparous female rabbits, we confirmed that these partially damaged nerves can be acutely depolarized, either at low (2–5 Hz) or medium (10–20 Hz) frequencies, to induce a proportional increase in urethral pressure. Evaluation of micturition volume in the mid-age multiparous animals after perineal nerve stimulation, effectively reversed a baseline deficit, increasing it 2-fold (p = 0.02). These results support the notion that selective neuromodulation of pelvic floor muscles might serve as a potential treatment for SUI.

Three-Dimensional Urethral Profilometry—A Global Urethral Pressure Assessment Method

Background: To present a new method of urethral pressure examination, and to evaluate diagnostic capabilities of three-dimensional profilometry, as an alternative to classical urethral profile (UPP). Using five channel catheters and dedicated software, a global urethral pressure image is obtained. The method eliminates the main limitation of classical urethral profilometry, where the catheter orientation determines the pressure picture limited to only one point in the urethral circumference; we observed up to 50% differences in pressure measures depending on the point of urethral circumference where the measurement was taken. Methods: This is a preliminary study containing a method presentation and analysis of the use in varied clinical cases of either healthy patients or patients with lower urinary tract symptoms (LUTS). The article includes a technique and equipment description and a full evaluation of selected cases, including three-dimensional urethral pressure distribution graphics. Results and Conclusions: Three-dimensional profilometry compared to the classical technique is comparable regarding the time, cost, technical difficulty and patient discomfort. At the same time, we obtained much more data on the urethral pressure and its distribution. The results are easy to interpret due to the 3D movable graphics created automatically by the dedicated software.

Secretomes of human pluripotent stem cell-derived smooth muscle cell progenitors upregulate extracellular matrix metabolism in the lower urinary tract and vagina

Background Adult mesenchymal stem cells (MSCs) have been studied extensively for regenerative medicine; however, they have limited proliferation in vitro, and the long culture time induces cell senescence. MSCs also contribute to tissue repair through their paracrine function. In this study, we sought to examine the paracrine effects of human smooth muscle cell progenitors (pSMC) on the urethra and adjacent vagina of stress urinary incontinence rodents. We use human pluripotent stem cell (PSC) lines to derive pSMCs to overcome the issue of decreased proliferation in tissue culture and to obtain a homogenous cell population. Method Three human PSC lines were differentiated into pSMCs. The conditioned medium (CM) from pSMC culture, which contain pSMC secretomes, was harvested. To examine the effect of the CM on the extracellular matrix of the lower urinary tract, human bladder smooth muscle cells (bSMCs) and vaginal fibroblasts were treated with pSMC-CM in vitro. Stress urinary incontinence (SUI) was induced in rats by surgical injury of the urethra and adjacent vagina. SUI rats were treated with pSMC-CM and monitored for 5 weeks. Urethral pressure testing was performed prior to euthanasia, and tissues were harvested for PCR, Western blot, and histological staining. Kruskal-Wallis one-way ANOVA test and Student t test were used for statistical comparisons. Results pSMC-CM upregulated MMP-2, TIMP-2, collagen, and elastin gene expression, and MMP-9 activity in the human bladder and vaginal cells consistent with elastin metabolism modulation. pSMC-CM treatment in the SUI rat improved urethral pressure (increase in leak point pressure compared to intact controls, p < 0.05) and increased collagen and elastin expression in the urethra and the adjacent vagina. Conclusion Conditioned media from smooth muscle cell progenitors derived from human pluripotent stem cells improved urethral leak point pressure and collagen and elastin content in the SUI rat. These findings suggest a novel therapeutic potential for PSC-based treatments for SUI and pelvic floor disorders where tissues are affected by collagen, elastin, and smooth muscle loss.