Human endothelial colony forming cells and mesenchymal progenitor cells form functional blood vessels and improve rat cardiac function after ischemia/reperfusion injury

Abstract

We showed previously that human endothelial colony forming cells (ECFC) combined with mesenchymal progenitor cells (MPC) form functional blood vessels in vivo. Here, we investigated whether ECFC+MPC could form functional vascular networks within ischemic myocardium, and whether this would improve cardiac function. Ischemia/reperfusion injury was induced in immune‐deficient rats by ligation of the left anterior descending coronary artery for 40 min. ECFC+MPC (2×106cells, 2:3 ratio) or PBS were injected into the ischemic myocardium after reperfusion. Luciferase‐labeled ECFC showed that 1,600 ECFC were present at day 14, indicating a quantifiable level of cellular retention. Perfused human ECFC‐lined vessels in myocardium were visualized at time points up to three months by femoral vein injection of fluorescently‐tagged human‐specific lectin. Left ventricular (LV) dimensions and heart weight to tibia length ratios were decreased in ECFC+MPC compared to PBS‐injected hearts at 4 months, suggesting that ECFC+MPC injection reduced LV hypertrophy. Pressure‐volume loop measurements showed that cardiac function was at least partially recovered in ECFC+MPC compared to PBS‐injection. Fibrosis area was not different between groups at 4 months. These data suggest that delivery of ECFC+MPC into ischemic myocardium to enhance neovascularization could be a therapeutic approach to restore cardiac function.