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Fig. 8 | Stem Cell Research & Therapy

Fig. 8

From: Mesenchymal stromal cells modulate the molecular pattern of healing process in tissue-engineered urinary bladder: the microarray data

Fig. 8

Mechanism of urinary bladder regeneration by activation of developmental hedgehog signaling pathway (1). The basal stem cells (A) within native urothelial layer give rise to (injury) activated urothelial (B) cells that rapidly proliferate and migrate on graft’s superficial layer to restore urothelial layer (2). The smooth muscle precursors (C) within detrusor muscle begin to populate the graft under the stimuli received from activated urothelium (3). There is a constant feedback in signaling between urothelium and smooth muscle cells (4). The mesenchymal stem cells (D) seeded on the graft’s surface (E) provide, at early stages of regeneration process, additional temporary stimulation mainly for urothelial stem cells (5). The expression of Hh ligands (mainly Shh) increases under MSCs’ stimuli in urothelial basal stem cells (6). Elevated Shh ligand concentrations are realized into regeneration environment (7). Shh ligand bind to membrane Ptch-Smo (smoothened) complex on smooth muscle precursors and activate it (8). Smo transduce signal by Gli transcription factor family that after activation relocate to cells’ nuclei and switch on the expression of target genes (9). The major Hh target gene products are Bmp and Wnt families of morphogens (10). Stem cell-seeded graft enhances expression of Bmp and Wnt proteins (11). Bmp mainly Bmp 4 and 1 and Wnt mainly Wnt 2 and 5 delivered paracrine stimulation to urothelium (a) and autocrine positive regulation (b) (12). The upregulated Hh pathway in stem cell-seeded graft support formation of new urothelial (a) and smooth muscle layer (b). This might be one of the important mechanisms responsible for better regeneration outcomes after using cell-based strategy to bladder reconstruction

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