Furthermore, the leak point pressure of cell-implanted rabbits is significantly higher than that of cell-free injected controls. We conclude that implantation selleck inhibitor of autologous bone marrow-derived cells could be an effective treatment for human post-surgical ISD-related urinary incontinence. We have been vigorously investigating regenerative medicine of the lower urinary tract based on tissue engineering and/or stem cell therapy techniques, both in vitro and in vivo.1–9 Tissue engineering strives to form functional tissues by using cells, scaffolds, and growth factors. Stem cell therapy
strives to restore functional structures by injections of adult somatic stem cells into damaged tissues. In this review, we show that implantation of autologous bone marrow-derived cells into injured urethral sphincters leads to the recovery of continence due to the replacement, enhancement, and/or reconstruction of the striated and smooth muscle layers. We group urinary incontinence into two
major categories: (i) stress urinary incontinence and (ii) post-surgical urinary incontinence associated with intrinsic sphincter deficiency (ISD). Stress urinary incontinence is an involuntary leakage of urine that occurs during physical activity, such as coughing, sneezing, or lifting heavy CHIR 99021 objects, and is the most common type.10,11 The majority of stress urinary incontinence cases is related to urethral hypermobility, which results from the loss of bladder neck support.12,13 Urethral hypermobility-related stress urinary incontinence can be improved by surgical therapies to lift the bladder and urethra.14,15 In contrast, post-surgical ISD-related urinary incontinence can occur as a result of radical prostatectomy16,17 or bladder neck surgery.18 It is characterized by severely decreased urethral closure pressure due to malfunction of the closure mechanism and results in intractable urinary incontinence.19 Under these circumstances, improvement of urinary continence requires increased urethral closure pressure. Injection of a bulking agent, such
as collagen, into the periurethral tissue has been widely accepted;20–23 however, the long-term benefits are not satisfactory because the continence rate sharply decreases with time.24,25 Surgical implantation of a device, such as an artificial urinary Metformin datasheet sphincter, has also been accepted as a treatment for this type of incontinence.26,27 However, this modality is not popular because the procedure is not covered by insurance. Additionally there are side-effects, such as inflammation and abscesses.28 Thus post-operative ISD-related urinary incontinence has few effective treatments. For that reason, we have vigorously investigated novel treatments that have proved to be effective in an experimental model of ISD-related urinary incontinence and have the potential to be effective in humans.