(Dr. Robert S. Cargill, advisor)

"The Effect of an In Vitro Mechanical Environment on the Proliferation and Phenotype of Bladder Smooth Muscle Cells"

Abstract

The urinary bladder is a mechanically active organ whose functioning is governed  by the presence of an appropriate mechanical environment.  In certain pathological situations, the mechanical environment of the bladder can change resulting in hypertrophy in the smooth muscle layer of the organ and loss of functionality. This study will examine the effects of mechanical environment on bladder smooth muscle cells in vitro by exposing cultures of rat bladder smooth muscle cells to different strain and strain rate combinations.  The first aim was to stretch the cells in a nutrient-rich environment and examine the effect of the stretch on proliferation rate and total DNA quantity, viability, and smooth muscle specific phenotype.  The results of this aim found that proliferation of the smooth muscle cells decreased in response to stretch and the expression of the phenotypic protein smooth muscle myosin increased.   The second aim was to stretch the smooth muscle cells in a nutrient-poor environment to simulate an environment that is more like what is seen in vivo.  Mechanical stretch increased both the proliferation rate and smooth muscle myosin expression for cells grown in the nutrient-poor environment. The final aim will be to modulate the stiffness of the smooth muscle cells to determine if the cells are responding to stress or strain in the in vitro mechanical environment.  Bladder smooth muscle cells were found to respond to stress when exposed to in vitro mechanical stretch. The findings from this study will aid in better understanding the changes that occur in smooth muscle cells during a bladder outlet obstruction.