Ureteral segmental replacement revisited

Background and Purpose: Long strictures of the proximal ureter are difficult to manage, and circumferential replacement with various natural and synthetic materials has been unsuccessful. We sought to use cultured autologous cells seeded onto graft material for proximal-ureteral replacement. Additionally, we wished to determine if urothelial cell-seeded de-epithelialized small bowel would generate adequate ureteral replacement. Materials and Methods: Three sets of experiments were performed. First, autologous pig-bladder smooth-muscle and urothelial cells were expanded in culture on large sheets of multilayer small-intestinal submucosa (SIS). These sheets were then tubularized and used to replace a 5-cm segment of proximal ureter in pigs. Second, autologous cells harvested from the bladders of Beagle dogs were cultured and seeded on porcine ureteral acellular matrix, which was used to replace a 3-cm segment of ureter in dogs. Segments were wrapped in omentum to enhance vascularity. Third, a de-epithelialized small-bowel segment seeded with autologous bladder-epithelial cells was transversally retubularized (Monti) into a 4-cm ureteral replacement. Follow-up studies consisted of retrograde pyelography, serum chemistry assays, hematoxylin/eosin studies, and immunohistopathologic examination using antibodies against alpha-smooth-muscle actin and pancytokeratin AE1-AE3. Results: Coculture of urinary-tract cells on large segments of SIS failed to create adequate ureteral replacement. All grafts were contracted and stenotic, with complete obstruction of the ipsilateral renal unit. Similar results were seen in the Beagles. Despite clinical obstruction and gross contraction of the graft, a circumferential muscular ureteral wall lined with multilayer transitional epithelium was present. Urothelium-seeded de-epithelialized Monti bowel segments resulted in patent ureteral replacement without hydroureteronephrosis and with normal renal function, serum electrolytes, and acid-base balance. However, bowel mucosa fully regenerated, with multilayer transitional epithelium growing adluminally in continuity with the proximal and distal anastomotic sites. Conclusions: Seeding of ureteral grafts with autologous bladder cells does not promote success in two large-animal models using different xenogenic acellolar matrices. However, muscle and urothelium regeneration occurs with ureteral acellular matrix in the dog. Urothelium-seeded de-epithelialized Monti bowel segments may be an acceptable substitute for long proximal ureteral segments. Further technical refinements are required to replace the bowel mucosa completely with normal urothelium.