An in vitro model of bladder smooth muscle cell function in response to select mechanical stimuli

• Main Author: Haberstroh, Karen Marie
• Format: Dissertation
• Language: English
• Subjects: engineering, biomedical; engineering, mechanical
• ISBN: 9780599739277; 0599739274

The bladder is a dynamic organ which responds to, functions under, and is controlled by mechanical forces. Elevated pressures within the bladder (resulting, for example, from either acute injury or obstruction) have been associated with hypertrophy of the bladder wall tissue, increased synthesis of extracellular matrix proteins, and subsequent loss of bladder tissue compliance. If this condition persists over many years, the mechanical and chemical consequences of increased bladder pressure and wall hypertrophy may contribute to clinical bladder pathologies, and ultimately to kidney damage and/or failure.
Little information currently exists regarding the effects of hydrostatic pressure and mechanical strain on bladder cell function, even though understanding the cellular responses to these mechanical stimuli is needed in order to develop novel therapeutic strategies with direct relevance to clinical practice. Novel in vitro cellular models were, therefore, designed to simulate conditions of the in vivo physiological and pathological mechanical environment of the bladder wall tissue, and examined the responses of bladder smooth muscle cells to either hydrostatic pressure alone, or to both mechanical strain and hydrostatic pressure simultaneously. Results of these studies provided the first cellular- and molecular-level evidence that exposure of bladder smooth muscle cells to these mechanical stimuli results in increased cell proliferation which is mediated by heparin binding-epidermal growth factor (HB-EGF), as well as in changes in the type and composition of extracellular matrix proteins (specifically, Collagen Type I and III).
In addition to offering insight into the cellular- and molecular-level mechanisms of bladder wall function, the results of the present study provided an explanation for clinical observations reported in the medical literature, in which pathological bladder conditions are accompanied by overall thickening of the bladder wall and decreased bladder tissue compliance. The same in vitro models were used to provide the first cellular-level evidence that kidney cell damage (which results from chronic bladder outlet obstruction in humans) may be related to both renal hypoxia and exposure to elevated hydrostatic pressure.
The novel in vitro models and related methodologies established by the present research endeavor could become the foundation for exploring and developing cellular- and molecular-level strategies (based on state-of-the-art pharmacological developments) which may become novel therapies for counteracting bladder wall tissue hypertrophy, decreased bladder compliance, and kidney damage/failure that results from chronic bladder outlet obstruction.