Abstract 18375: Cardioprotection by Cardiosphere-Derived Cells Administered 20 Min After Reperfusion in Rats: Reductions of Infarct Size, Apoptosis, and Macrophage Infiltration, Accompanied by Improved Function
Introduction: Cardiosphere-Derived Cells (CDCs) have been shown to reduce scar size following an established myocardial infarction (CADUCEUS Trial). It is currently unknown whether CDCs confer acute cardioprotection following ischemic injury. Here we test the hypothesis that intracoronary infusion of CDCs following ischemia/reperfusion (I/R) injury reduces cardiomyocyte stress, and protects against cardiac dysfunction and infarct expansion.
Methods & Results: Wistar-Kyoto rats (aged 8-12 weeks) underwent 45 minutes of ischemia and 20 minutes of reperfusion. Animals were then randomly allocated to either CDC or placebo groups and treated with 5x105 CDCs or PBS, respectively. Two days following I-R injury, CDC-treated rats revealed a reduction in percent infarct mass relative to PBS-treated controls (6.3% vs. 13.6%, p<0.01 n=5/group). These findings were accompanied with reduced programmed cell death within the infarct zone at day 2 (cleaved caspase 3, TUNEL positivity; p<0.05), and improved cardiac function at day 14 (EF: 45% vs. 62% p<0.01). While no difference was observed in peripherally circulating inflammatory cells, a reduction in CD68+ macrophages (Mϕ) was found within the myocardium of CDC-treated animals (23% vs. 18%, p<0.05; n=4/group). In vitro co-culture of CDCs with TNF-α-stimulated Mϕ cells attenuated the expression of IL-6, while concomitantly elevating IL-10, Tgfb1, and Arg1, gene expression profile within Mϕ cells (p<0.05).
Conclusions: Collectively, these data demonstrate that intracoronary infusion of CDCs following I/R produce acute cardioprotection, and confer prolonged myocardial integrity. Furthermore, CDCs reduce infarct expansion at 2 days and improve cardiac function at 14 days. The cardioprotective effects of CDCs involve a reduction in infiltrating, cytotoxic Mϕ cells.
- © 2013 by American Heart Association, Inc.