RECONSTRUCTION OF THE URINARY-BLADDER MUCOSA IN 3-DIMENSIONAL COLLAGEN GEL CULTURE - FIBROBLAST-EXTRACELLULAR MATRIX INTERACTIONS ON THE DIFFERENTIATION OF TRANSITIONAL EPITHELIAL-CELLS

The purpose of this study was to reconstruct a urinary bladder mucosa in three-dimensional collagen gel culture conditions that included fib roblasts. Transitional epithelial cells and fibroblasts, isolated resp ectively from the epithelial and lamina propria layers of porcine urin ary bladder, were cultured in monolayer. These fibroblasts were embedd ed and cultured within a collagen gel matrix to reconstruct a lamina p ropria. The isolated transitional epithelial cells were then seeded in vitro on this reconstructed lamina propria on which the transitional epithelial cells formed a stratified urothelium composed of basal, int ermediate and superficial layers. Urothelial differentiation was obser ved only on the fibroblast-containing collagen matrix. Differentiation did not occur on a cell-free collagen matrix through use of fibroblas t conditioned medium. Thus, urothelial differentiation depended upon a fibroblast-extracellular matrix interaction. The differentiated trans itional epithelial cell layer thus produced closely resembled a urothe lium in vivo. This culture model may provide a useful system in which to study various diseases of the urinary bladder.