Fig. 5

The healing process of tissue-engineered urinary bladder. 1. Shortly after bladder reconstruction with an in vitro constructed graft, urothelial (a) and detrusor cells (b) dedifferentiate into actively proliferating cells that migrate into the graft, populate it, and restore the neobladder wall. Simultaneously, as a part of healing process, fibroblasts begin to proliferate and form initial scar tissue (c) to limit the injury site. Even though precursors of smooth muscle cells elongate within the graft (d), their initial layered architecture is disrupted. The regenerated detrusors (e) characterizes with irregular smooth muscle bundle arrangement. The intestinal cells play an unknown role during bladder wall regeneration. They might however regulate restoration of the neuronal compartment of the bladder wall by interacting with regenerating neurons (f) at different time points after reconstruction. The inflammatory response comprises an initial acute phase and a subsequent chronic phase. The acute phase lasts from hours to days and is mediated mainly by neutrophilic reactions (g). Monocytes are then called into the site, and these differentiate into macrophages that are primary cells maintaining the chronic phase (h). 2. Differentially expressed pathways in bladders reconstructed with BAM seeded with or without ASCs at 7, 30, 90, and 180 days postoperatively. The most crucial signaling pathways for each period are provided. Active carcinogenic pathways are marked with red