Abstract
ObjectivesTo evaluate the regenerative potential of human dental pulp stem cells (hDPSCs) in an animal model of stress urinary incontinence (SUI). SUI, an involuntary leakage of urine, is due to physical stress involving an increase in bladder pressure and a damage of external urethral sphincter affecting muscles and nerves. Conventional therapies can only relieve the symptoms. Human DPSCs are characterized by peculiar stemness and immunomodulatory properties and might provide an alternative tool for SUI therapy.Materials and methodsIn vitro phase: hDPSCs were induced towards the myogenic commitment following a 24 hours pre‐conditioning with 5‐aza‐2′‐deoxycytidine (5‐Aza), then differentiation was evaluated. In vivo phase: pudendal nerve was transected in female rats to induce stress urinary incontinence; then, pre‐differentiated hDPSCs were injected in the striated urethral sphincter. Four weeks later, urethral sphincter regeneration was assayed through histological, functional and immunohistochemical analyses.ResultsHuman DPSCs were able to commit towards myogenic lineage in vitro and, four weeks after cell injection, hDPSCs engrafted in the external urethral sphincter whose thickness was almost recovered, committed towards myogenic lineage in vivo, promoted vascularization and an appreciable recovery of the continence. Moreover, hDPSCs were detected within the nerve, suggesting their participation in repair of transected nerve.ConclusionsThese promising data and further investigations on immunomodulatory abilities of hDPSCs would allow to make them a potential tool for alternative therapies of SUI.
Highlights
Urinary incontinence (UI), defined as the involuntary leakage of urine, affects 200 million people worldwide, with prevalence in‐ creasing with age, increases rate of skin infection and has significant psychosocial and economic burdens, leading to significant quality of life issues.Urinary incontinence arises from dysfunctions affecting the pel‐ vic floor, whose physiology is maintained by a fine balance among bone, muscle and nerve tissues.The three most common types of UI are stress urinary incon‐ tinence (SUI), urge urinary incontinence (UUI) or a combination of both, that is mixed urinary incontinence (MUI)
While the former is caused by a weakness in the pelvic floor musculature, pelvic fascia and pubourethral liga‐ ments, the latter is caused by pudendal nerve damage and damage to the intrinsic and extrinsic urethral sphincter, as occurring in men after radical prostatectomy.[2]
The most important factors that may trigger the onset of stress urinary incontinence are pregnancies, obesity and menopause, while in men SUI is mainly associated with surgical iatrogenic lesions
Summary
Urinary incontinence (UI), defined as the involuntary leakage of urine, affects 200 million people worldwide, with prevalence in‐ creasing with age, increases rate of skin infection and has significant psychosocial and economic burdens, leading to significant quality of life issues. While the former is caused by a weakness in the pelvic floor musculature, pelvic fascia and pubourethral liga‐ ments, the latter is caused by pudendal nerve damage and damage to the intrinsic and extrinsic urethral sphincter, as occurring in men after radical prostatectomy.[2] These two injuries affecting striated muscle and nerve fibres are strongly correlated with the SUI.[3] For the prevention of male stress incontinence resulting from radical prostatectomy, some researchers have proposed intraoperative re‐ constructive techniques such as the posterior musculofascial recon‐ struction[4] or the pubo‐prostatic ligament reconstruction.[5] Surgical approaches, such as tension‐free vaginal tape, transobturator slings or pubovaginal slings, remain the gold stan‐ dards for SUI treatment. The aim of our study was to investigate whether hDPSCs are able to restore the urethral sphincter to normal histology and function in female rats after inducing SUI through pudendal nerve resection
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