Abstract 731: Persistence and Efficacy of Intra-Coronary Injected Endothelial Progenitor Cells in a Porcine Model of Myocardial Infarction
Introduction - MRI can track stem cells following intramyocardial injection. However, clinically these cells are often given intracoronary (IC). It is not known if this diffuse distribution of cells can be imaged with MRI.
Hypotheses - That MRI can longitudinally track the distribution of IC delivered cells. The persistence of these cells results in improved LV function.
Methods - In 7 pigs (5 active, 2 controls), MI was induced by 90 minute balloon occlusion of the LAD. Bone marrow was aspirated and the endothelial progenitor cell (EPC) fraction purified and cultured. 7–14 days following MI, EPCs were colabeled with an iron-fluorophore (Bangs particle) and a fluorescent cell viability marker (CMTMR). They were delivered to the LAD via an inflated over the wire PTCA balloon. T2*-weighted images (FGRE) assessed the location of the cells’ magnetic label at days 0, 7 and 42. The heart was explanted, cut into short axis slices and the gross distribution of fluorescences was assessed using a Kodak Multi-modal imager. Intracellular colocalization of both fluorescent dyes was assessed with confocal fluorescent microscopy.
Results - Immediately following cell delivery, hypointensity characteristic of the cells’ magnetic label was observed in the infarct border rather than within the infarct itself. The ratios of the signal intensity of cells/normal tissue (±SD) were: day 0 0.573±0.14; 1 week 0.894±0.06; 6 weeks 0.839±0.12. At 6 weeks the signal hypointensity appeared more within the infarct itself rather than infarct border region. There was a trend for improved ejection fraction (EF) amongst the cell-treated animals: EF in cell-treated animals 30.7 ± 5.5% → 34.8 ± 3.0%; EF in control animals 30.5 ± 1.3% → 28.5 ± 7.8%. Post-mortem fluorescent imaging showed concordance of the cells’ fluorescent labels with the regions of hypointensity seen on MRI, and confocal fluorescent microscopy revealed intracellular colocalization of both fluorescent dyes.
Conclusions -MRI can longitudinally track the persistence and distribution of magnetically labeled EPCs following IC delivery. Signal hypointensity declines with time. These cells appear to migrate from border regions of infarction into the infarct region itself. Delivery of these cells appears safe and may improve LVEF.