PL 21. Effect of periurethral injection of autologous adipose-derived stem cells on stress urinary incontinence rat model
Stress urinary incontinence (SUI) is a prevalent urological problem that is common in women. Up to 50% of women older than 60-yearold have symptoms of stress or urge urinary incontinence. The female urethra is comprised of a fibromuscular system containing muscle cells, elastic fibers, collagen fibers, and reticular fibers. The different properties of these component structures lead to a balance between extensibility and mechanical resistance. Disruption of these components may influence urethra closing pressure and hence provoke incontinence, although precise mechanisms are a topic of continuing investigation.
Contemporary therapeutic approaches for the SUI are not intended to alter the physiological function of the urethra and instead rely on placement of foreign materials4,5. Urethral slings are effective for many cases of SUI but are not universally successful and carry risks of complications. Stem cell therapy is a promising modality that may be used to replace, repair, or enhance the biological function of damaged tissue or organs. Whether this might be applied to the problem of SUI is an intriguing.
To investigate the effect of injected autologous adiposederived stem cells (ADSCs) on stress urinary incontinence (SUI) in a rodent model of parturition--related stress incontinence he rat SUI model was developed by postpartum balloon dilation of the vagina to simulate prolonged labor followed by bilateral ovariectomy. ADSCs were isolated from the periovarian fat and labeled with thymidine analog 5-ethynyl-2-deoxyuridine (EdU). Twenty rats received periurethral injection of phosphatebuffered saline (PBS) as the negative controls and the other 20 rats received periurethral injection of EdU-labeled ADSCs. Twenty control rats underwent sham ovariectomy without balloon dilation and served as positive controls. Four weeks later, voiding function was assessed by cystometry. Urethra histological examination (Masson's trichrome stain, picrosirius red stain, Hart's elastin stain, Gordon & Sweet's stain and immunohistochemical stain) and Western blot were performed on urethral tissues.
Both leak point pressure (LPP) and bladder capacity were significantly increased in ADSC-treated rats, compared with the balloon-injured ovariectomized rats. Histological examination revealed normalized appearance of the fibromuscular structure of the urethra as well as increased periurethral blood vessel density in ADSC-treated rats. On Western blot, VEGF and P-ERK1/2 protein was expressed at a higher rate in tissues from ADSCtreated rats compared to SUI rats.
Periurethral injection of ADSC could restore urinary function by altering pathological changes of SUI, which might be mediated by regulating the activity of VEGF and ERK1/2.