Abstract 16967: Preclinical Evaluation of Biopolymer-Delivered Endothelial Progenitor Cells in Hibernating Myocardium
Background: Vasculogenic cell-based therapy combined with tissue engineering is a promising revascularization solution for patients with hibernating myocardium (HM), a common clinical condition. However, large animal studies are lacking and we therefore used a clinically relevant pig model of HM to examine the benefits of endothelial progenitor cells (EPCs) and biopolymer therapy in this context. We hypothesized that the delivery of EPCs within a matrix would yield greater improvements in myocardial blood flow (MBF), metabolism, and function than EPCs alone or PBS control.
Methods: Twenty-three Yorkshire swine underwent placement of an ameroid constrictor on the left circumflex artery (LCx). After 2 weeks, animals underwent echocardiography, a rest and a dipyridamole-induced stress 13N-NH3 PET scan, and a rest 18FDG-PET viability scan. At the same time, EPCs were isolated and cultured for 1 week, and swine were randomized to intramyocardial injections (total: 3 ml) of PBS (n=9), EPCs (∼30 x 106; n=7), or EPCs + a collagen-based matrix (n=7). PET imaging was repeated 4 weeks post treatment, and swine were sacrificed the following week.
Results: Hibernation was detected in 60% of animals and was specific to the LCx region (p=0.002). Baseline MBF was reduced at rest and stress in the affected region, compared to the remote area (1.13 ± 0.09 vs. 1.57 ± 0.15 ml/min/g at stress, respectively, p=0.01). At follow-up, MBF at stress and myocardial flow reserve (not shown) were higher in the EPC + matrix group compared to EPCs or PBS (EPCs + matrix: +21 ± 13%; EPCs -17 ± 8%; PBS: +5 ± 10%, p<0.05). This was paralleled by improved wall motion abnormalities (EPCs + matrix by 30 ± 9 %; EPCs by 22 ± 21%; PBS by 15 ± 12 %) and improved mismatch scores (EPCs + matrix by 79 ± 10%; EPCs by 55 ± 15%; PBS by 35 ± 19%)(all p<0.05). MBF at stress in the LCx segments positively correlated with smooth muscle actin staining for arterioles (r=0.7; p=0.02).
Conclusions: This preclinical swine model successfully demonstrated the creation of HM, which was improved by vasculogenic cell therapy. The additional effects conferred by a collagen-based delivery matrix over EPCs alone included improved MBF in the EPC + matrix group, as well as circulatory and metabolic recovery with improvements in myocardial function.
- © 2011 by American Heart Association, Inc.