Effect of cardiosphere-derived cell administration on cardiac function after myocardial infarction: influence of the delivery route in a relevant porcine model
V Crisostomo, C Baez Diaz, A Torrescusa, V Alvarez, M Pulido, E Lopez, F M Sanchez MargalloAbstract
Introduction
Several studies suggest that cardiosphere-derived cells (CDCs) may improve cardiac function by increasing viable myocardial tissue and limiting adverse ventricular remodeling. On the other hand, evidence indicates that the delivery route may modulate the effect of cell therapy. The aim of this study was to comparatively evaluate the efficacy of CDC administration through either the intracoronary (IC) or intrapericardial (IP) route in a porcine model of reperfused myocardial infarction (MI).
Methods
This blinded, randomized study was approved by the institutional animal care and use committee. Twenty-six female Large White pigs were used to establish a reperfused myocardial infarction via transient occlusion (90 minutes) of the LAD immediately distal to the first diagonal branch. Surviving animals were randomized into three groups: control (n = 8), IC (n = 8), and IP (n = 8). At a mean of 4 days after MI induction, 30 × 10⁶ CDCs were administered via the IC or IP route in the treated groups. Control animals received saline IC (n=4) or IP (n=4). IP administration was performed through a left lateral mini-thoracotomy, and IC delivery via percutaneous femoral artery access. Cardiac function was assessed by cardiac magnetic resonance imaging (CMR), including late gadolinium enhancement, immediately before therapy administration and at 10 weeks. Left ventricular ejection fraction (LVEF), indexed end-diastolic and end-systolic volumes (EDVi and ESVi), infarct size, and treatment effects (defined as the change in these parameters from baseline to 10 weeks) were calculated. Values are expressed as mean (S.E.M). Results were compared using Kruskal–Wallis ANOVA and the Mann–Whitney test.
Results
All animals received therapy or placebo in absence of complications or electrocardiographic abnormalities regardless of the delivery route. The measured CMR parameters are summarized in the table. As no significant differences were observed between control subgroups, control animals were pooled for analysis. At the end of follow-up (10 weeks), LVEF was significantly higher in both treated groups compared with controls (p = 0.04). Similarly, the treatment effect on LVEF (ΔLVEF) differed among the three groups (p = 0.04), due to a significant difference between the control and IP groups. No other significant differences were found among groups in either ventricular volumes or IS, nor were there any additional differences related to the delivery route.
Conclusions
Administration of 30 × 10⁶ CDCs via either the IP or IC route in a porcine model of reperfused MI may slightly but significantly improve cardiac function compared to placebo, regardless of the delivery route, which suggests that the approach could be tailored to the specific clinical circumstances with equal efficacy.Abstract table