Intravenous Injection of hMSCs Improves Cardiac Function in Mice with Pressure-Overload-Induced Heart Failure
(A) Experimental design for hMSC delivery into the transverse aortic constriction (TAC) model. hMSCs were injected at a concentration of 5.0 × 105 cells per body via the tail vein. The injection was repeated 6 times at 2- to 3-day intervals within a period of 2 weeks. Echocardiography was performed at day 14. (B) Serum exosomes were subjected to western blot analysis with the indicated antibodies of exosome markers (n = 3–4). (C–H) Comparison of heart tissue of WT mice with or without injection of hMSCs at 2 weeks after TAC or sham surgery. (C) Representative images of echocardiography. (D) Ejection fraction (EF) and fractional shortening (FS) measured at 2 weeks after TAC or sham surgery (n = 4–6). (E) Heart weight per tibia length ratio (n = 4–6). (F) Relative expression of heart failure markers of the indicated mice (n = 7–8). (G) Representative images of hematoxylin and eosin (H&E)-stained and wheat germ agglutinin (WGA)-stained sections of the apical heart (scale bars, 50 mm). (H) Myocyte cross-sectional area (CSA) calculated by BZ-X analyzer software (n = 3). Data are mean ± SEM. All experiments in this figure were tested in two separate trials. ∗p < 0.05; ∗∗p < 0.01; ∗∗∗p < 0.001 versus sham. ††p < 0.01; †††p < 0.001 between groups, by one-way analysis of variance with post hoc Tukey’s multiple comparisons.