Obstructive uropathy is a common cause of pediatric end-stage renal disease. Despite physicians best efforts at managing the sequelae of bladder outlet obstruction, adaptive changes to the pediatric bladder often occur. Though initially beneficial, hypertrophic tissue remodeling of bladder smooth muscle in response to stimuli such as obstruction and denervation eventually becomes maladaptive. Patients ultimately suffer from either a small fibrotic high-pressure bladder or an atonic, non-contractile bladder (Figure 1). Beyond the risk of injury to renal function in these cases, these patients also suffer from the physical and social ramifications of incontinence and urinary tract infection. Unfortunately, the signals that underlie tissue remodeling at the molecular level are poorly understood (Adam 2006, Review) and no pharmacologic interventions to limit the fibroproliferative remodeling exist. Current research regarding bladder regeneration deals primarily with replacement of the end-stage bladder, primarily attempting to develop tissue engineered constructs to restore bladder storage capabilities (Drewa 2012, Review Article). These constructs may utilize stem cells obtained from embryos or bone marrow, however, none have functioned appropriately as a normal bladder, both storing urine at low pressures and emptying efficiently. I propose research to harness the inherent stem cells within the bladder to stimulate the bladder’s natural regenerative capacity. Resident bladder stem cells could potentially prevent loss of bladder function or restore function in those children whom bladder function has already deteriorated. Furthermore, understanding the signaling pathways behind functional deterioration of bladder smooth muscle may lead to earlier detection of patients who will ultimately develop bladder and kidney problems.
|Effective start/end date||4/1/14 → 3/31/19|
- Hartwell Foundation (Agmt. Rcvd. 4/1/14)
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