M yocardial hibernation is a common clinical condition affecting patients with advanced coronary artery disease, 1 for whom cell-based therapies are targeted. In hibernation, repetitive episodes of ischemia and reperfusion lead to metabolic and functional changes in cardiomyocytes, ultimately impairing left ventricular (LV) function. Current therapies such as coronary artery bypass grafting or percutaneous coronary intervention are well established but not suitable for all patients; in previous clinical research from our group, more than one third of patients referred for revascularization did not undergo intervention because of unsuitable vessel anatomy, comorbidities, or other reasons.1 These patients are at high risk of cardiac events, and novel approaches such as cell-based vasculogenic therapy could provide them with an alternative form of therapy.
Clinical Perspective on p 991Circulating angiogenic cells (CACs) constitute a heterogeneous population of peripheral blood-derived fibronectincultured cells. Although what defines their phenotype is still debated, 2 they were shown to uptake acetylated low-density lipoprotein, bind Ulex europaeus agglutinin-1 lectin, and express the pan-leukocyte marker CD45. They can also stain positive for monocyte/macrophage (CD14, CD11b/Mac-1, and CD11c) and endothelial (vascular endothelial growth factor receptor 2, von Willebrand factor, vascular endothelialcadherin, and CD31) markers. [3][4][5] Transplanted cells likely contribute to neovascularization through a paracrine mechanism by secreting and recruiting cardioprotective or proangiogenic growth factors. 6,7 The revascularization potential of Background-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. Methods and Results-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 resu...