Funding outcome

Pediatric urology clinics are inundated with children suffering from abnormal bladders. It commonly presents with varying severity in the newborn with renal failure, spina bifida, and posterior urethral valves. Despite this frequency, however, our current treatment protocols remain crude and minimally effective. Our most severely affected patients are forced to empty their bladder by passing a catheter every 3-4 hours. This poses risk of recurrent bladder and kidney infections and obviously provides a huge burden to the patients and their care-givers. Spina bifida is one of the most severe congenital birth anomalies. Although the primary defect involves the spinal cord, there is subsequent morbidity that occurs across multiple organ systems. However, throughout childhood and adolescence, the urinary tract becomes a primary source of morbidity and embarrassment. This defect is characterized by abnormal innervations of the bladder which results in a hyperactive bladder and closed sphincter, termed Fixed Partial Bladder Outlet Obstruction. Consequently, there is frequent urinary incontinence and urinary tract infections, and if left untreated, leads to permanent bladder damage and kidney failure. Current clinical interventions include intermittent urethral catheterization, taking drugs and surgically increasing the bladder size. All of these are very crude, and result in significant morbidity. Therefore, the current research is focusing on finding effective means of preventing bladder damage and improving the quality of life of these vulnerable children. Adult stem cells are a type of cells that have a high ability to expand, repair tissue damage and can be manipulated to grow into many cell types of the body. A unique advantage of using stem cells as a therapy is that it can be derived from the patient's own body, expanded in the lab and given back to the same patient. Thus, significantly reducing side effects and complications associated. This project will test the ability of stem cells to either protect bladder tissues from obstruction-induced damage or reverse/repair such damages using animal models. This study has a potential of identifying a novel therapy to improve bladder conditions of children born with spina bifida and will form the basis for further clinical studies of stem cell therapy to treat bladder complications associated with spina bifida and posterior urethral valves . Our past research, using both animal experimentation and tissue culture techniques, has highlighted the role of oxygen. These abnormal bladders cannot empty and suffer from high pressures resulting in decreased blood flow and cells of the bladder that do not receive sufficient oxygen. This starts a cascade of inflammatory changes which result in a hyperactive response from the muscles, and eventual death of the tissue and scar formation. Recently, we have been experimenting with stem cells to prevent the inflammation and scar formation in bladder cells and have excellent results. Moving on, we would like to use a new gene and protein analysis technique to confirm the effectiveness of stem cell therapy in an animal model (rats) of overactive bladder. Then we will look for new proteins with the potential to treat the bladder condition.This work has great potential to progress to human applications; The basic understanding and excellent animal results will lay the foundation towards larger animal studies and human trials. Any significant improvement in our treatment of these abnormal bladders will improve the health and quality of life of these afflicted children.