Human-umbilical cord matrix mesenchymal cells improved left ventricular contractility independently of infarct size in swine myocardial infarction with reperfusion

Figure 1. Study flowchart.

Figure 2. Doppler-derived coronary flow velocity. At the end of the injection, APV was higher in vehicle injected animals (with and without MI), as compared to hUCM-MSC (26.8 ± 6.8 vs. 20.5 ± 4.5; ANOVA p = 0.03). In infarcted animals injected with hUCM-MSC, final APV did not decrease significantly as compared do baseline (20.3 ± 4.5 vs. 21.5 ± 3.6; Related samples Wilcoxon Signed rank test p = 0.25). Symbols represent geometric means and bars represent standard deviation. APV, average peak velocity; T1/2—half time injection.

Figure 3. Representative images of transthoracic echocardiogram. Bidimensional images (A) in infarcted animals show apical akinesia (white arrow) and reduced wall thickness. In M-mode (B) measurements of Interventricular septum thickness (yellow), left ventricular cavity dimension (white) and left ventricular lateral wall thickness (green) are indicated at end-diastole and end-systole (ED and ES, respectively). Notice the dilation in AMI pigs, marked wall dyskinesia (indicated by arrows) and reduced systolic wall thickening. An example of speckle tracking longitudinal strain analysis is shown (C).

Figure 4. (A) Invasive hemodynamic parameters and (B) representative pressure-volume loops of vehicle-injected sham (sham + vehicle), vehicle-injected myocardial infarction (AMI + vehicle), and umbilical cord stromal cell-injected myocardial infarction pigs (AMI + hUCM-MSC). End-systolic and end-diastolic pressure-volume relationships are plotted on the left upper and right lower corner of the loops, respectively. Bars represent mean and standard deviation. p-values are described for all comparisons between groups. PRSW, preload recruitable stroke work.

Figure 5. Semi-automated quantification of infarct size. Triphenyl tetrazolium chloride (TTC) staining (A,B) and Quantification of interstitial fibrosis and cardiomyocyte hypertrophy in the remote myocardium (Panels C–F). In Panels B,E,F, bars represent the average (and standard error) of all hearts in each group. Symbols (***) denote significant differences between groups (p < 0.05). Differences favoring AMI-hUC-MSC vs. AMI-vehicle were not statistically significant.

Figure 6. Active (A) and passive (B) length-tension relationship in isolated skinned cardiomyocytes from the remote myocardium. AT, active tension; PT, passive tension. *p < 0.05 for the comparison of sham vs. placebo: **p < 0.05 for the comparison of sham vs. cells. Regarding the comparisons of passive tension between groups (Panel B), p-values ranged between 0.57 and 0.99.

Figure 7. Transcriptional alterations in the remote myocardium after UCM-MSC delivery. (A) Principal component analysis (PCA) plot showing the segregation of samples according to gene expression profiles. (B) Total number of differentially expressed genes between the 3 groups. (C) Volcano plot of MI + Vehicle vs. MI + UCM-MSC comparison with upregulated genes in MI + UCM-MSC colored in red and downregulated genes colored in green. (D) Heatmap depicting up and downregulated genes in MI + UCM-MSC. (E) Gene ontology enrichment analysis of Biological Processes upregulated in MI + vehicle, organized by false discovery rate (FDR) score.