Preclinical Evaluation of Biopolymer-Delivered Circulating Angiogenic Cells in a Swine Model of Hibernating Myocardium

Abstract

Vasculogenic cell-based therapy combined with tissue engineering is a promising revascularization approach targeted at patients with advanced coronary artery disease, many of whom exhibit myocardial hibernation. However, to date, no experimental data have been available in this context; we therefore examined the biopolymer-supported delivery of circulating angiogenic cells using a clinically relevant swine model of hibernating myocardium. Twenty-five swine underwent placement of an ameroid constrictor on the left circumflex artery. After 2 weeks, animals underwent echocardiography, rest and stress ammonia-positron emission tomography perfusion, and fluorodeoxyglucose positron emission tomography viability scans. The following week, swine were randomized to receive intramyocardial injections of PBS control (n=10), circulating angiogenic cells (n=8), or circulating angiogenic cells+collagen-based matrix (n=7). The imaging protocol was repeated after 7 weeks. Baseline positron emission tomography myocardial blood flow and myocardial flow reserve were reduced in the left circumflex artery territory (both P<0.001), and hibernation (mismatch) was observed. At follow-up, stress myocardial blood flow had increased (P≤0.01) and hibernation decreased (P<0.01) in the cells+matrix group only. Microsphere-measured myocardial blood flow validated the perfusion results. Arteriole density and wall motion abnormalities improved in the cells+matrix group. There was also a strong trend toward an improvement in ejection fraction (P=0.07). In this preclinical swine model of ischemic and hibernating myocardium, the combined delivery of circulating angiogenic cells and a collagen-based matrix restored perfusion, reduced hibernation, and improved myocardial wall motion.