Regeneration of Bladder Urothelium, Smooth Muscle, Blood Vessels and Nerves Into an Acellular Tissue Matrix

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Abstract
To study the cellular events occurring during bladder development and regeneration we developed an in vivo model of bladder augmentation with an acellular tissue graft. We propose that the extracellular matrix orchestrates the regenerative capacity of host bladder cells (urothelium, smooth muscle, blood vessels and nerve cells) after bladder augmentation with acellular tissue matrix. A total of 40 adult rats underwent partial cystectomy and augmentation with a patch of extracellular matrix representing the full thickness of rat gastric or bladder tissue. Sections were examined histologically to assess urothelial, smooth muscle and neuronal invasion of the graft. A total of 32 rats was evaluated 1 day to 26 weeks after grafting. Epithelialization occurred by day 4, accompanied by granulocytic infiltration. Smooth muscle regenerated 2 weeks after grafting in juxtaposition to epithelial surfaces and it matured into normal sized bundles by 26 weeks. Neovascularity was noted 2 weeks postoperatively. Neural elements formed around developing smooth muscle bundles as early as 4 weeks after grafting. We demonstrated the regeneration of urothelium, smooth muscle, blood vessels and nerves within a full thickness grafted acellular tissue matrix scaffold in the rat. The spatial orientation of these elements suggests that mesenchymal-epithelial interactions occur during phenotypic regeneration of the bladder. Urothelium appears to regulate the early forming smooth muscle. This in vivo model provides a suitable method to study cellular events during regeneration.