Stem cell-based regeneration therapies in stress urinary incontinence: Mechanisms, innovation, and challenges.

Stress urinary incontinence (SUI) is characterized by the involuntary leakage of urine from the urethra due to increased abdominal pressure. The complex pathophysiological mechanisms underlying SUI have driven the development of diverse therapeutic strategies. Current treatment options encompass both conservative and surgical interventions, with surgical approaches generally often regarded as the most effective option approach for severe cases. However, many surgical techniques carry significant risks of complications. In this context, urethral injection therapy, primarily based on stem cell-mediated regenerative approaches, has emerged as a minimally invasive alternative. Stem cell therapies leverage their multipotent differentiation capacity and paracrine signaling pathways to directly target the pathophysiological contributors to SUI, including urethral sphincter dysfunction, neuromuscular junction degeneration, and imbalances in elastin and collagen homeostasis. This narrative review provides a critical evaluation of current stem cell-mediated regenerative strategies for SUI, focusing on cellular mechanisms and the therapeutic effects driven by paracrine signaling. Recent clinical advances, unresolved scientific controversies, and innovative combinatorial delivery systems incorporating targeted therapeutic approaches are analyzed. Despite challenges remain, such as determining the optimal stem cell dosage and improving in vivo survival rates, ongoing research offers valuable insights into the development of cell-free bioactive derivatives, advanced combination delivery systems, and precise molecularly targeted therapies.