Cultured bladder cells and their response to mechanical strain.

Abstract

The mechanism responsible for the transformation of a normal bladder into a poorly compliant storage vesicle is not well understood. However, a common feature of many poorly compliant bladders is an abnormal accumulation and distribution of matrix proteins within the bladder wall1–4. Histological examination of tissues from bladders with outlet obstruction is frequently associated with infiltration of connective tissue2. This abnormal accumulation is uniquely associated with the muscle bundles of the detrusor layer and has been shown by immunohistochemistry to be largely composed of type III collagen4. Biochemical studies of myelodysplastic bladders show this characteristic fibrosis to result from a quantitative increase in type III collagen5. Since these same bladders have altered compliance, we believe that the loss of elasticity is related to the changed collagen composition of the bladder wall. A common link in pathological conditions with poor bladder compliance is premorbid exposure of the bladder wall and its constituent cells to an abnormal physical environment, e.g., uncontrolled intermittent contractions. The impact of this abnormal environment upon bladder function is difficult to assess in whole bladder studies. It is likewise difficult to assess the relative contributions of the various tissue components within the bladder wall to the overall loss of compliance. We have previously isolated and maintained and characterized fetal bovine bladder urothelial, fibroblastic and smooth muscle cells in culture6–8. To begin to understand the role of mechanical forces in altering synthesis of connective tissue proteins and assess the relative responses of the individual cell types found in the bladder wall, we have applied equibiaxial deformations to the three major cell types found in the bladder wall9.