Abstract 9912: Global Intracoronary Infusion of Allogeneic Atrial Cardiosphere-Derived Cells (CDCs) Stimulates Myocyte Regeneration and Reverses LV Remodeling in Miniature Swine With Chronic Myocardial Infarction
Background: Intracoronary infusion of autologous CDCs (icCDCs) into the infarct-related artery using the “stop flow” technique improves regional function in patients but global function remains unchanged. We tested the hypothesis that this reflects the inability to regress cellular hypertrophy and replace myocytes lost in remote remodeled regions that can be overcome by global intracoronary infusion of CDCs.
Methods: Miniswine (n=10) were studied 8 weeks after chronic infarction was produced by LAD microembolization (1x106 microspheres, 45μm diameter). Ejection fraction decreased from 63 ± 2% at baseline to 31 ± 2% four weeks after infarction (p<0.05 vs. baseline) and remained unchanged at 8 weeks (32 ± 2%, p-ns vs. 4 weeks). Allogeneic CDCs (20 x 106 CDCs, cyclosporine 100 mg/day) isolated from donor atrial biopsies were infused into the 3 major coronary distributions without interrupting flow. We assessed myocardial function (echo), myocyte proliferation (Ki67) and infarct size (TTC) in comparison to untreated controls. Regional myocyte regeneration was quantified by assessing myocyte nuclear density and size.
Results: Infusing icCDCs into infarcted and remodeled remote myocardium increased regional function and ejection fraction (Table). icCDCs stimulated myocyte proliferation (Ki67) in LAD and remote regions by three-fold. As a result, myocyte number (nuclear density) increased by 35% and myocyte cell diameter decreased by 33% in both LAD and remote myocardium. The reduction in infarct volume after icCDCs was not significant.
Conclusion: We conclude that global infusion of allogeneic icCDCs without “stop flow” 1.) stimulates myocyte proliferation throughout the LV and 2.) in a model of infarction, improves regional function with a substantial increase in left ventricular ejection fraction. Thus, allogeneic icCDCs may afford a widely available platform to reverse LV dysfunction in patients with chronic post infarction LV remodeling.
- Cardiac regeneration
- Regenerative medicine stem cells
- Myocardial infarction
- Stem cell therapy
- Ischemic heart disease
- © 2013 by American Heart Association, Inc.