Urinary incontinence is a major health care problem in the United States. The NIDDK has recently convened a workshop to bring attention and foster research in this underserved area. This grant will explore and develop a novel and promising treatment of urinary incontinence. The investigators will explore in depth the role of cellular tissue engineering using myoblast and muscle derived cells as a treatment of stress urinary incontinence when injected into the urethra. In addition, myoblast injection may improve detrusor contractility when injected into the bladder wall. They will also develop cell mediated gene therapy for the lower urinary tract using autologous muscle derived cells. The investigators hypothesize that: 1. Myoblast injection can improve bladder and urethral smooth muscle function. 2. Autologous myoblast can be harvested and injected to achieve long-term success. 3. Cell mediated gene therapy using myoblasts transduced with trophic factors can further repair urinary tract muscle damage. 4. Myoblast engineered with adenovirus carrying the expression for nitric oxide synthase gene can increase NO release and improve inflammatory cystitis and reduce bladder outlet obstruction. This grant explores the frontier of tissue engineering and gene therapy for the treatment of urinary tract dysfunction. The investigators believe that this project has direct clinical utility in the near future. Based on their anticipated results, they propose to harvest autologous muscle derived stem cells by aspirating a very small amount of skeletal muscle from a patient's arm. Grow the muscle derived cells in culture and engineered these myoblasts with viruses carrying the expression of growth and trophic factors or nitric oxide synthase [sic]. The engineered myoblasts are then injected into the impaired urethra or bladder of that patient during a simple outpatient cystoscopic procedure.
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