Bladder regeneration with cell-seeded small intestinal submucosa

This study was performed to determine the regenerative properties of smooth muscle cells (SMCs) and urothelial cells (UCs) seeded on small intestinal submucosa (SIS), utilizing a nude mouse model. Human bladder SMCs and UCs were seeded on SIS in a layered coculture fashion. Cell-seeded SIS grafts (1 x 1 cm(2)) were maintained in a CO2 incubator for 14 days and subsequently folded with the seeded cells facing the lumenal side and implanted subcutaneously into the flanks of nude mice (n = 20). Unseeded SIS grafts were implanted into the contralateral flanks of the mice to serve as controls. Grafts were harvested at 4, 8, and 12 weeks after implantation. By 12 weeks, layered urothelium with a central lumen was noted with early smooth muscle bundle formation peripherally. At each time point, the regenerated SMCs stained positive for alpha-smooth muscle actin, and the UCs stained positive for cytokeratin AE1/AE3. The control group demonstrated no evidence of organized bladder regeneration. This study demonstrates the potential for cell-seeded SIS to induce organized bladder regeneration in vivo. This also provides the basis for additional work utilizing seeded SIS grafts for bladder augmentation.