Abstract
Background: Previously we reported that global infusion of CDCs in infarcted and non-infarcted remote regions improved LV function in swine with chronic myocardial infarction. The effect of global infusion of CDCs on angiogenesis and myocyte regeneration in infarcted and non-infarcted remote regions is unknown. Methods: Swine (n=11) with chronic infarction in the left anterior descending (LAD) coronary artery region were studied 8 weeks after microsphere embolization (1x10^6 particles, 45μm diameter). CDCs were isolated from myocardial atrium and 20 x 10^6 CDCs were infused into the 3 major coronary distributions after cyclosporine (100mg/day) immunosuppression. Data were compared to untreated animals. To assess the factors related to angiogenesis, VEGF and SDF-1 expression on cultured CDCs were quantified by RT-PCR. Angiogenesis was quantified by assessing capillary density (von Willebrand Factor) with immunohistochemistry. Myocyte regeneration was quantified by assessing myocyte nuclear density. The ratio of capillary density to myocyte nuclear density was evaluated. Results: icCDCs improved infarcted LAD (13±6 vs. 36±6%, p<0.05) and remote (47±8 vs. 99±10%, p<0.05) wall thickening with increased ejection fraction (32±3 vs. 45±4%, p<0.05) compared to untreated. RT- PCR from cultured CDCs showed VEGF expression and to a less extent SDF-1 expression. icCDCs increased capillary density and myocyte nuclear density in infarcted LAD and remote regions by 40% (Table). Thus, the ratio of capillary density to myocyte nuclear density was maintained in untreated and icCDCs animals. Conclusion: These data indicate that in a model of infarction, global infusion of icCDCs stimulates angiogenesis and myocyte regeneration to the same extent in infarcted and non-infarcted regions resulting in improved global function. Thus, global infusion of icCDCs may afford a widely available approach to regenerate myocardium in patients with ischemic cardiomyopathy.
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