Abstract 1271: Preservation of Left Ventricular Function and Attenuation of Remodelling After Transplantation of Human Epicardium-Derived Cells into the Infarcted Mouse Heart
Background: Proper development of compact myocardium, coronary vessels and Purkinje fibers depends on the presence of epicardium-derived cells (EPDCs) in the embryonic myocardium. We hypothesise that adult human EPDCs (hEPDCs) can reactivate the embryonic program when transplanted into ischemic myocardium, thereby improving cardiac performance after myocardial infarction (MI).
Methods: hEPDCs were isolated from human atrial tissue. By LAD-ligation, a MI was created in NOD/scid mice, immediately followed by intramyocardial injection of 4*105 hEPDCs labelled with eGFP (n=17) or culture medium only (n=14). Infarct size (after 2 days) and left ventricular function (after 2 and 14 days) were assessed using a 9.4 T animal-MRI. Data were analysed using dedicated software. Excised hearts were used for immunohistochemical analysis.
Results: After correction for infarct size, ejection fraction (EF) on day 2 did not differ between groups (hEPDC: 29.2±1.5% vs. medium: 27.7±1.7%, p=n.s.), but EF on day 14 was significantly higher in the hEPDC-injected group (hEPDC: 25.9±1.3% vs. medium 12.7±1.4%, p<0.001). End-systolic volume (ESV) and end-diastolic volume (EDV) were significantly smaller in the hEPDC-injected group, both on day 2 (ESV-hEPDC: 40.0±2.0μl vs. ESV-medium: 49.7±2.3 μl, p<0.05; EDV-hEPDC: 56.3±2.3 μl vs. EDV-medium: 68.5±2.6μl, p<0.05) and on day 14 (ESV-hEPDC: 87.1±5.8μl vs. ESV-medium: 122.8±6.4μl, p=0.001; EDV-hEPDC 116.5±5.6μl vs. EDV-medium: 140.1±6.2μl, p<0.05). Immunohistochemistry showed massive engraftment of injected hEPDCs at day 15, which expressed the smooth muscle cell marker α-smooth muscle actin (1A4), the endothelial cell marker vWF, and sarcoplasmic reticulum Ca2+-ATPase (SERCA2a). Cells were negative for the cardiomyocyte markers cTnI and ANF. Preliminary observations indicated a higher capillary density and an increased wall thickness of the infarcted area in the hEPDC-treated group compared to the medium-treated group.
Conclusions: After transplantation in ischemic myocardium, human EPDCs acquired a myo-endothelial phenotype, preserved cardiac function, and attenuated remodelling. Autologous hEPDCs are promising candidates for clinical application in injured hearts.