Abstract 19074: Multi-Vessel Intracoronary Infusion of Allogeneic Cardiosphere-Derived Cells in a Porcine Model of Myocardial Infarction

Abstract

Background: Single-vessel, intracoronary cardiosphere derived cells (CDCs) have been shown to be safe and effective in both preclinical and clinical studies. However, the potential utility of multivessel intracoronary delivery to target global left ventricular remodeling post-myocardial infarction (MI) has not been studied. Objective: We sought to evaluate the safety and efficacy of multivessel intracoronary delivery of allogeneic CDCs in a porcine model of subacute MI. Methods: MI was created in adult female Yucatan minipigs. Three weeks later, 12.5M allogeneic CDCs were infused sequentially in each of the three coronary vessels; LAD, LCX and RCA under stop-flow (Group 1) or nonocclusive-flow conditions (Group 2). Animals infused with vehicle under stop flow conditions served as the control group (Group 3; n=5 per group). Animals underwent MR imaging at baseline (just before infusion) and 4 weeks post-infusions. Left ventricular ejection fraction, scar mass and viable mass were evaluated at both time points. Results: Ejection fraction (EF) did not differ among the three groups at baseline. However, LV function was better preserved in both CDC infusion groups compared to vehicle at 1 month follow-up (ΔEF=-4+/-1.6% in Group 1, p=0.13; ΔEF =-1.1+/-2.2% in Group 2, p=0.7; ΔEF=-4.6+/-2.3% in Group 3, p=0.05). In terms of scar mass, CDCs under both stop-flow and non-occlusive infusion technique reduced 1 month post-treatment compared to the vehicle group (Δscar mass= -2.9+/-0.6gr in Group 1, p=0.012; Δscar mass= -1.2+/- 0.4gr in Group 2, p=0.028; Δscar mass =-1.9+/-1.1gr in Group 3, p=0.16). Viable mass was not changed significantly in any of the groups (p=ns). No humoral response (by circulating antibodies) or additional cell inflammatory response (by histopathological analysis) were detected 1 month post infusion in the continuous flow CDCs group. Serum troponin I measured at 24 hrs was routinely elevated in the stop-flow group, but not in the nonocclusive flow group. Conclusions: Nonocclusive multivessel delivery of allogeneic CDCs is safe and effective to preserve left ventricular function as soon as 1 month post-delivery, paving the way for future applications targeting global left ventricular remodeling.