Fig. 5. Cell therapy-reduced disease associations and -nullified adverse effects validated in vivo.

a Ingenuity Pathway Analysis (IPA) interrogation of the infarction altered proteome for cardiovascular disease annotations revealed enriched functions (57 gray bars, p < 0.001), of which only 15 remained in the cell therapy altered proteome (red asterisks). b In IPA Tox Function analysis, hypergeometric overrepresentation predicted 24 cardiac adverse effects associated with the infarcted proteome (gray), 20 of which were significant (p < 0.05). Following interpretation of the reversed subproteome, nearly all adverse effects were predicted to be nullified by cell therapy (red). c–e Infarcted animals were randomized to those without (MI) versus those receiving cardiopoietic (CP) cell therapy (MI + CP), and assessed by echocardiography and electrocardiography for cardiac structure c, electrophysiology d and contractility e. Ischemic cardiomyopathy (MI, n = 8) was characterized by left ventricular dilation and pump failure, quantified by increased end-systolic volume c and decreased ejection fraction e, respectively, 4 weeks post- relative to pre-randomization. In contrast, CP cell therapy (MI + CP, n = 16) reversed infarction induced cardiac enlargement c and improved performance e. QT prolongation, a parameter of ventricular repolarization associated with tachyarrhythmia, observed in MI (n = 8) was blunted in MI + CP (n = 8; d). Bars in c–e indicate standard error of the mean.