IPSC-derived human cardiac progenitor cells improve ventricular remodelling via angiogenesis and interstitial networking of infarcted myocardium.

ABSTRACT: We investigate the effects of myocardial transplantation of human induced pluripotent stem cell (iPSC)-derived progenitors and cardiomyocytes into acutely infarcted myocardium in severe combined immune deficiency mice. A total of 2 × 10(5) progenitors, cardiomyocytes or cell-free saline were injected into peri-infarcted anterior free wall. Sham-operated animals received no injection. Myocardial function was assessed at 2-week and 4-week post-infarction by using echocardiography and pressure-volume catheterization. Early myocardial remodelling was observed at 2-week with echocardiography derived stroke volume (SV) in saline (20.45 ± 7.36 ?l, P < 0.05) and cardiomyocyte (19.52 ± 3.97 ?l, P < 0.05) groups, but not in progenitor group (25.65 ± 3.61 ?l), significantly deteriorated as compared to sham control group (28.41 ± 4.41 ?l). Consistently, pressure-volume haemodynamic measurements showed worsening chamber dilation in saline (EDV: 23.24 ± 5.01 ?l, P < 0.05; ESV: 17.08 ± 5.82 ?l, P < 0.05) and cardiomyocyte (EDV: 26.45 ± 5.69 ?l, P < 0.05; ESV: 18.03 ± 6.58 ?l, P < 0.05) groups by 4-week post-infarction as compared to control (EDV: 15.26 ± 2.96 ?l; ESV: 8.41 ± 2.94 ?l). In contrast, cardiac progenitors (EDV: 20.09 ± 7.76 ?l; ESV: 13.98 ± 6.74 ?l) persistently protected chamber geometry against negative cardiac remodelling. Similarly, as compared to sham control (54.64 ± 11.37%), LV ejection fraction was preserved in progenitor group from 2-(38.68 ± 7.34%) to 4-week (39.56 ± 13.26%) while cardiomyocyte (36.52 ± 11.39%, P < 0.05) and saline (35.34 ± 11.86%, P < 0.05) groups deteriorated early at 2-week. Improvements of myocardial function in the progenitor group corresponded to increased vascularization (16.12 ± 1.49/mm(2) to 25.48 ± 2.08/mm(2) myocardial tissue, P < 0.05) and coincided with augmented networking of cardiac telocytes in the interstitial space of infarcted zone.

SUBMITTER: Ja KP 

PROVIDER: S-EPMC4727567 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature