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.
Please cite this paper as: Callewaert G, Albersen M, Janssen K, Damaser MS, Van Mieghem T, van der Vaart CH, Deprest J. The impact of vaginal delivery on pelvic floor function -delivery as a time point for secondary prevention: a commentary. BJOG 2016;123:678-681. Pelvic floor disorders (PFD) cover a spectrum of conditions, including pelvic organ prolapse (POP), urinary (UI) and fecal incontinence (FI). Vaginal birth is considered the leading risk factor. Passage of the fetal head is associated with exceptional forces on and stretching of the pelvic floor. Since vaginal delivery occurs under medical supervision, it is the ideal moment for preventive action.1 Measures could be initiated promptly, restoring the damage caused by vaginal delivery to prevent PFD from developing. One of the experimental strategies currently being explored is the use of stem cells to boost the innate healing response. Though apparently futuristic, the experimental evidence of its efficacy is accumulating. The deleterious effects of childbirth on the pelvic floorAlthough PFD is a multifactorial disease there is ample evidence that vaginal delivery (VD) causes pelvic floor trauma. These mechanisms are believed to be essentially mechanical and ischaemic in nature. The impact of VD on the anal sphincter has been long recognised. The prevalence of anal sphincter injury following VD as visible on ultrasound is as high as 24.5% in prospective studies.2 VD makes the pubococcygeal muscles stretch to at least twice their initial length.3 In experimental conditions in non-pregnant rabbits, stretching a skeletal muscle by half its length is already sufficient to cause function loss. 4 Whether this threshold also applies to the levator and the peripartum is uncertain, but it should be no surprise that there is clinically demonstrable levator trauma following VD in one out of three women. 5VD also damages the innervation of the pelvic floor. The anal sphincter as well as the levator plate innervation may be injured by stretch, although for levator injury, compression and ischaemia may also contribute. 6 As a consequence, 40% of women display increased pudendal nerve terminal motor latency, although this recovers in two-thirds of women.7 Electromyography of the levator ani muscle has shown neuropathic injury in one quarter of women after a single VD, though that study did not correlate the observed changes to pelvic floor function. 8The urethral rhabdomyosphincter is too small for reliable electromyography; nonetheless, a reduction in urethral closure pressure after vaginal delivery has been shown, though not confirmed by other studies. 9There should be no doubt that VD leads to immediate measurable damage, but only in a minority of the cases does this lead to immediate loss of function or symptoms. Over time, however, up to half of women who delivered vaginally display PFD, as recently documented in several large studies. By a unique combination correlating obstetrical factors concerning first delivery and long-term anatomical and functional outc...
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