Stress Incontinence in the Era of Regenerative Medicine: Reviewing the Importance of the Pudendal Nerve

Purpose: Regenerative medicine will likely facilitate improved stress urinary incontinence treatment via the restoration of its neurogenic, myogenic and structural etiologies. Understanding these pathophysiologies and how each can optimally benefit from cellular, molecular and minimally invasive therapies will become necessary. While stem cells in sphincteric deficiency dominate the regenerative urology literature, little has been published on pudendal nerve regeneration or other regenerative targets. We discuss regenerative therapies for pudendal nerve injury in stress urinary incontinence. Materials and Methods: A PubMed (R) search for pudendal nerve combined individually with regeneration, injury, electrophysiology, measurement and activity produced a combined but nonindependent 621 results. English language articles were reviewed by title for relevance, which identified a combined but nonindependent 68 articles. A subsequent Google Scholar (TM) search and a review of the references of the articles obtained aided in broadening the discussion. Results: Electrophysiological studies have associated pudendal nerve dysfunction with stress urinary incontinence clinically and assessed pudendal nerve regeneration functionally, while animal models have provided physiological insight. Stem cell treatment has improved continence clinically, and ex vivo sphincteric bulk and muscle function gains have been noted in the laboratory. Stem cells, neurotrophic factors and electrical stimulation have benefited pudendal nerve regeneration in animal models. Conclusions: Most regenerative studies to date have focused on stem cells restoring sphincteric function and bulk but whether a sphincter denervated by pudendal nerve injury will benefit is unclear. Pudendal nerve regeneration appears possible through minimally invasive therapies that show significant clinical potential. Treating poor central control and coordination of the neuromuscular continence mechanism remains another challenge.