AN IN-VITRO MODEL OF UROTHELIAL REGENERATION - EFFECTS OF GROWTH-FACTORS AND EXTRACELLULAR-MATRIX PROTEINS

Although the cellular turnover of resting urothelium is very low, its regenerative capacity is known to be outstanding. In organotypic mouse urothelial cultures closely mimicking the differentiation and multila yering of normal urothelium, we examined the cell biological mechanism s underlying urothelial regeneration and the specific role of growth f actors and several extracellular matrix (ECM) components. Exposure to epidermal growth factor (EGF) and acidic fibroblast growth factor (aFG F) and culture on laminin resulted in enhanced expansion of the urothe lium. Microscopy and assessment of proliferative activity revealed tha t enhanced urothelial expansion due to EGF could be attributed to incr eased proliferative activity and an increase in cell numbers, whereas aFGF-stimulated expansion must be considered the consequence of increa sed cellularity and migration. Laminin-enhanced urothelial expansion w as shown to be the result of spreading of the entire urothelial organo typic culture. This was associated with a considerable decrease in the number of cell layers. A synergistic effect of growth factors and lam inin was not found. This organotypic urothelial cell culture model see ms to be very useful in studying strategies to improve urothelial rege neration.