Ther Adv Urol. 2015 Feb;7(1):22-40. doi: 10.1177/1756287214553968.
The potential role of stem cells in the treatment of urinary incontinence.
1Glickman Urological and Kidney Institute, The Cleveland Clinic, USA.
2The Cleveland Clinic, Department of Biomedical Engineering, 9500 Euclid Avenue ND20, Cleveland, OH 44195, USA.
Voiding dysfunction encompasses a wide range of urologic disorders including stress urinary incontinence and overactive bladder that have a detrimental impact on the quality of life of millions of men and women worldwide. In recent years, we have greatly expanded our understanding of the pathophysiology of these clinical conditions. However, current gold standard therapies often provide symptomatic relief without targeting the underlying etiology of disease development. Recently, the use of stem cells to halt disease progression and reverse underlying pathology has emerged as a promising method to restore normal voiding function. Stem cells are classically thought to aid in tissue repair via their ability for multilineage differentiation and self-renewal. They may also exert a therapeutic effect via the secretion of bioactive factors that direct other stemand progenitor cells to the area of injury, and that also possess antiapoptotic, antiscarring, neovascularization, and immunomodulatory properties. Local injections of mesenchymal, muscle-derived, and adipose-derived stem cells have all yielded successful outcomes in animal models of mechanical, nerve, or external urethral sphincter injury in stress urinary incontinence. Similarly, direct injection of mesenchymal and adipose-derived stem cells into the bladder in animal models of bladder overactivity have demonstrated efficacy. Early clinical trials using stem cells for the treatment of stress urinary incontinence in both male and female patients have also achieved promising functional results with minimal adverse effects. Although many challenges remain to be addressed prior to the clinical implementation of this technology, novel stem-cell-based therapies are an exciting potential therapy for voiding dysfunction.
mechanism of action; mesenchymal stem cells; overactive bladder; regenerative medicine; secretome; systemic therapy; tissue engineering;urinary incontinence
Cytotherapy. 2010;12(1):88-95. doi: 10.3109/14653240903350265.
Treatment of stress urinary incontinence with adipose tissue-derived stem cells.
1Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, California, USA.
Effective treatment for stress urinary incontinence (SUI) is lacking. This study investigated whether transplantation ofadipose tissue-derived stem cells (ADSC) can treat SUI in a rat model.
Rats were induced to develop SUI by postpartum vaginal balloon dilation and bilateral ovariectomy. ADSC were isolated from the peri-ovary fat, examined for stem cell properties, and labeled with thymidine analog BrdU or EdU. Ten rats received urethral injection of saline as a control. Twelve rats received urethral injection of EdU-labeled ADSC and six rats received intravenous injection of BrdU-labeled ADSC through the tail vein. Four weeks later, urinary voiding function was assessed by conscious cystometry. The rats were then killed and their urethras harvested for tracking of ADSC and quantification of elastin, collagen and smooth muscle contents.
Cystometric analysis showed that eight out 10 rats in the control group had abnormal voiding, whereas four of 12 (33.3%) and two of six (33.3%) rats in the urethra-ADSC and tail vein-ADSC groups, respectively, had abnormal voiding. Histologic analysis showed that the ADSC-treated groups had significantly higher elastin content than the control group and, within the ADSC-treated groups, rats with normal voiding pattern also had significantly higher elastin content than rats with voiding dysfunction. ADSC-treated normal-voiding rats had significantly higher smooth muscle content than control or ADSC-treated rats with voiding dysfunction.
Transplantation of ADSC via urethral or intravenous injection is effective in the treatment and/or prevention of SUI in a pre-clinical setting.
Keywords: Adipose tissue-derived stem cells, urethra, stress urinary incontinence, conscious cystometry, transplantation