FoxC1-Induced Vascular Niche Improves Survival and Myocardial Repair of Mesenchymal Stem Cells in Infarcted Hearts

Figure 5

FoxC1 contributes to MSC therapy-induced angiogenesis in the adFoxC1 IHs. (a) FoxC1 mRNA expression in PBS or MSC-treated IHs in the presence/absence of FoxC1 transfection/knockdown. (b–d) mRNA expression of Ang-1 (b), bFGF (c), and VEGF (d) in the CON IHs, the adFoxC1 IHs, or the siFoxC1 IHs after cell therapy. (e) FoxC1, Ang-1, bFGF, and VEGF protein expression in the IHs treated with PBS or MSCs in the presence/absence of adFoxC1/siFoxC1. In the IHs, MSC therapy upregulated FoxC1, Ang-1, bFGF, and VEGF expression compared with PBS injection; FoxC1 pretransfection improved their expression, whereas siFoxC1 abolished it. (f) FoxC1 improvement of angiogenesis induced by MSC therapy in the adFoxC1 IHs was determined by the number of factor VIII positive-staining vessels per mm² under high-power field view. (g, h) Representative images of VEGF (g, red, ) or factor VIII (h, red, ) staining of cardiomyocytes and vessels in the infarct and peri-infarct areas from the MSC-treated IHs in the presence/absence of adFoxC1/siFoxC1. The nuclei were stained with DAPI and revealed as blue. VEGF was mainly expressed by the blood vessels and cardiomyocytes in the MSC-treated IHs, especially in the animals that had received MSCs combined with FoxC1 transfection. Similarly, the greatest vascular density can be seen in the MSC-treated adFoxC1 IHs. All graphical data are the . vs. PBS in the CON IHs, ^† vs. MSCs in the CON IHs, ^‡ vs. PBS in theadFoxc1 group, ^§ vs. MSCs in the adFoxc1 IHs, and ^|| vs. PBS in the siFoxc1 IHs (CON IHs: PBS, , and MSCs, ; adFoxc1: PBS, , and MSCs, ; siFoxC1: PBS , and MSCs, ); Student’s -test.