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The Role of Genetically Modified Mesenchymal Stem Cells in Urinary Bladder Regeneration

Fig 2

Effects of Cyr61 and Wnt5a on regenerating vasculature and musculature.

(A) Cyr61OX and Wnt5aOX showed early and persistent increased vasculature, comparably greater than unmanipulated MSCs, with numbers of vessels/mm2 similar to MSC/CD34+ HSPC grafts at 4 weeks. (§ Unseeded, MSC and MSC/CD34+ HSPC data, shown as solid and dotted lines, previously reported [7]). At both 4 and 10 weeks, Cyr61KD demonstrated significantly decreased vasculature as compared to Cyr61OX. Data shown as means ± SEM; ***P<0.001 for Cyr61KD vs Cyr61OX. (B) Wnt5aOX demonstrated mean muscle content most comparable to MSC/CD34+ HSPC grafts [percent red (muscle): (red (muscle) pixels / red (muscle) + blue (collagen) pixels)]. (§ Unseeded, MSC and MSC/CD34+ HSPC data, shown as solid and dotted lines, previously reported [7]). Cyr61KD demonstrated a significant decrease in muscle percentage from 4 to 10 weeks (p<0.05), with levels significantly lower than Cyr61OX at both time points. Data shown as means ± SEM; *P<0.05 and **P<0.01 for Cyr61KD vs Cyr61OX. (C) Sample photomicrographs of Masson’s trichrome staining demonstrate differences in muscle/collagen content and level of vasculature (marked with black arrows) between Cyr61KD and the Cyr61OX and Wnt5aOX groups. Density score was greatest for Wnt5aOX at 4 weeks. Scale bar, 50 μm. (Unseeded, MSC and MSC/CD34+ HSPC images shown in S1 Fig).

Fig 2

doi: https://doi.org/10.1371/journal.pone.0138643.g002