Epithelium-free bladder wall graft: epithelial ingrowth and regeneration--clinical implications for partial cystectomy.

PURPOSE: Most patients who need a bioengineered bladder wall have bladder cancer. A graft made with autologous urothelium would not be safe. To investigate the feasibility of providing bioengineered tissue for patients with partial cystectomy we evaluated the host and graft response after transplanting an epithelium-free graft. MATERIALS AND METHODS: De-epithelialized bladder wall grafts from male rats were transplanted on syngeneic female rat bladders after partial cystectomy. Urothelial morphology, vessel density, inflammation, stromal thickness and uroplakin expression were evaluated 1, 3, 6 and 9 months after surgery. Cell gender was distinguished by fluorescent in situ hybridization using unique X and Y chromosome probes. RESULTS: There was no significant graft contraction at any time. Male graft urothelial morphology and uroplakin expression were similar to those of controls at all time points. The donor bladder had decreased vessel density at early time points while the host had increased vascularity, which normalized in each by 6 months. Graft inflammation and edema normalized by 9 months. There was no muscular hypertrophy. Fluorescence in situ hybridization revealed early ingrowth of host female urothelium and a small fraction of male urothelial cells, which appeared between 1 and 3 months. CONCLUSIONS: Within 9 months de-epithelialized grafts appeared histologically as normal bladder, surprisingly faster than an equivalent model with full-thickness grafts. The safety and function of an epithelium-free graft must be determined in a large animal model. These early data in a small animal model substantiate the feasibility and equivalency of using grafts without epithelium, which would allow application in patients with cancer.