Abstract 19374: A Collagen Matrix for Endothelial Progenitor Cell Therapy Improves Myocardial Function through Enhanced Cell Retention and Phenotype in a Mouse Model of Myocardial Infarction
Background: To improve cell therapy, we tested the echo-guided intramyocardial delivery of Endothelial Progenitor Cells (EPCs), with and without a collagen matrix, in a mouse model of myocardial infarction (MI). We studied the potential role of the matrix on enhancing cell retention and phenotype, as well as on myocardial perfusion, viability, and function.
Methods: Seven days after left anterior descending coronary artery ligation in female C57BL6/J mice, animals were randomly allocated to receive echo-guided intramyocardial injection of: EPCs (n=21), Matrix alone (n=13), EPCs+Matrix (n=22), or PBS (n=8). EPCs were green fluorescent protein (GFP)+ marrow derived cells from C57BL/6-Tg(CAG-EGFP)1Osb/J male mice. 13N-ammonia and 18F-FDG PET imaging, as well as echocardiography, were performed at baseline and 3 weeks after treatment.
Results: Post-MI baseline ejection fraction (EF) was equivalent in all groups (pooled average=36%). Follow-up EF was significantly greater in the EPC+Matrix group (56.6±3%) compared to EPC (36.7±3%), Matrix (34.9±5%) and PBS (29.4±4%) groups (p<0.001). PET analysis showed increases in viability (6.5±3.1%, p=0.09) and perfusion (4.5±2.3%, p=0.10) in the EPC+Matrix group 3 weeks after treatment delivery, compared to baseline. Histology showed an anterior to posterior (control) LV wall thickness ratio of 0.68±0.07 in EPC+Matrix group, which was significantly more than for all other groups (EPC:0.26±0.02, Matrix:0.22±0.03, PBS:0.12±0.01; p<0.01). More arterioles were detected in hearts injected with EPC+Matrix (16±0.8 per field of view (FOV)) compared to EPC (11±0.9), Matrix (8±0.8) and PBS (5±0.7) (p<0.001). Moreover, there was higher intramyocardial retention of GFP+ cells co-expressing von Willebrand factor in EPC+Matrix group, compared to the EPC group (67±21 versus 10±6 cells per FOV; p=0.03).
Conclusions: Intramyocardial delivery of EPCs within a collagen matrix improves cardiac function, partially restores myocardial viability and perfusion, preserves LV wall mass, and enhances transplanted cell retention and phenotype in a mouse MI model. These mechanisms conferred by a delivery matrix have potential implications for the understanding and optimization of cardiac cell therapy.
- Myocardial infarction
- Cardiac regeneration
- Stem cell therapy
- Endothelial progenitor cell
- Positron emission tomography
- © 2010 by American Heart Association, Inc.