Abstract 334: Intracoronary Allogeneic Mesenchymal Stem Cells and Cardiosphere-Derived Cells Exert Comparable Effects on Myocyte and Capillary Proliferation Without Promoting Functional Arteriogenesis in Swine With Chronic Myocardial Ischemia
Objective: Allogeneic icMSCs and icCDCs each improve function of hibernating myocardium but the underlying mechanisms remain unclear. We performed the present study to assess the effects of icMSCs and icCDCs on myocardial perfusion and remodeling of the coronary microcirculation in a large animal model of chronic regional ischemia.
Methods: Cyclosporine-treated swine (200 mg/day) with hibernating myocardium from a chronic LAD stenosis received ~35 x 106 icMSCs, ~35 x 106 icCDCs, or vehicle. Regional function (echocardiography), adenosine-vasodilated perfusion (microspheres) and vascular remodeling were assessed 1-month after treatment.
Results: Baseline LAD wall thickening (%WT) was reduced in all animals ( LAD 38 ± 2% vs. 83 ± 5% in remote, p<0.01) but not different between treatment groups. Coronary flow during vasodilation was also critically reduced at baseline (LAD 2.4 ± 0.3 ml/min/g vs. 4.6 ± 0.3 ml/min/g in remote, p<0.01). Intracoronary stem cell infusion improved LAD %WT but did not alter vasodilated perfusion (Table). Although capillary density increased in relative proportion to the increase in myocyte number, there were no significant changes in arteriolar density following cell therapy.
Conclusion: These data demonstrate that the functional improvement afforded by allogeneic icMSCs and icCDCs is accompanied by concomitant capillary angiogenesis and myocyte regeneration in hibernating myocardium. However, myocardial perfusion deficits persist due to an inability of either cell type to promote functional arteriogenesis, indicating that cell therapy-mediated functional benefits occur independently of changes in coronary blood flow.
Author Disclosures: B.R. Weil: None. G. Suzuki: None. M.M. Leiker: None. B.A. Palka: None. J.A. Fallavollita: None. J.M. Canty Jr: None.
This research has received full or partial funding support from the American Heart Association.
- © 2014 by American Heart Association, Inc.