Plasticity of the urothelial phenotype: Effects of gastro-intestinal mesenchyme/stroma and implications for urinary tract reconstruction

The present study tests the hypothesis that heterotypic stromal-epithelial interactions cause phenotypic changes in urothelium. The rational for the e xperimental design is to simulate heterotypic stromal-epithelial interactio ns that are created at the anastomotic site of intestinal-bladder augmentat ions and internal urinary diversions where the urothelium is in direct cont act with the gastro-intestinal tract tissues. Tissue recombination experiments were performed by combining 14-day embryon ic rat and mouse rectal mesenchyme with urothelium from embryonic, newborn, and adult mice or rats. All tissue recombinants were grown beneath the ren al capsule of athymic mouse hosts for 6-16 weeks. Analyses were performed t o detect expression of uroplakins, cytokeratin 7, 14, 19 and mucin secretin g epithelial cells via Periodic Acid-Schiff (PAS). The phenotype of both mo use and rat urothelium was changed to a glandular morphology under the infl uence of rectal mesenchyme. Immunohistochemical staining revealed a loss of the urothelial specific uroplakins and cytokeratins 7, 14, and 19 (charact eristic of urothelium). Histologic analysis revealed the presence of mucin secreting glandular structures which stained positive for PAS. The urotheli al transdifferentiation into glandular epithelium was not a function of epi thelial age and occurred in the embryonic, newborn and adult urothelium. Li kewise, rectal mesenchyme from embryonic, neonatal, and adult animals was a ble to induce glandular differentiation in bladder epithelium. Urothelium exhibits the plasticity to change into an intestinal like epithe lium as a result of mesenchymal/stromal stimulation from the gastro-intesti nal tract. This experimental result is germane to heterotypic stromal-epith elial interactions that are created in patients with urinary tract reconstr uctions (intestinal augmentations, de-mucosalized urothelial lined bladder patches, and internal urinary diversion such as ureterosigmoidostomies). We propose that heterotypic stromal-epithelial interactions may play a role i n determining histodifferentiation of urothelial cells at the anastomotic s ite between bowel and bladder tissue in patients with gastro-intestinal uro thelial reconstructions.