Abstract 143: Evaluation of the Paracrine Effect of Encapsulated Mononuclear Stem Cells in the Acute Myocardial Rat Model

Abstract

Many studies have considered stem cell-based therapy as a treatment option for acute myocardial infarction (AMI). Paracrine signaling has been proposed as an underlying mechanism, in which released cytokines and chemokines may promote angiogenesis and activation of resident stem cells. In order to characterize this paracrine action, bone marrow mononuclear stem cells (BM-MNC) collected from femur of adults GFP+ Wistar rats were encapsulated in 1.5% of sodium alginate. Animals were randomized in three groups: SHAM (n=3); Empty capsules (n=8); BM-MNC capsules (n=8). AMI was induced by permanent occlusion of the left anterior descending artery after anesthesia with 100mg/kg ketamin and 10 mg/kg xylazine. Soon after the AMI, capsules (empty or BM-MNC) were delivered intra-thoracically. SHAM group was submitted to the same surgical procedures without permanent artery occlusion or treatment given. Troponin I (cTnI) was measured 24h after AMI in order to evaluate the success of the procedures; echocardiography was also performed to assess heart morphofunctional parameters 48h and 7 days after AMI. At day 7, after echocardiography, the animals were euthanized under profound anesthesia (isoflurane 5%) and their hearts were withdrawn for biochemical analysis. Plasma and tissue levels of TNF-α and IL-6 were measured by ELISA. All technical procedures were performed by blinded operators. Statistical comparisons were made using ANOVA analysis followed by Tukey post-test or using t-Student test when appropriated. BM-MNC were viable after day 7 since GFP+ cells were detected by fluorescence microscopy. Nevertheless, the empty capsules groups showed lower levels cTnI compared to BM-MNC group (25 vs. 40 ng/mL, respectively; p=0.03). There was no difference in the shortening fraction (24% VS. 18%, respectively; p=0.08) and in the infarcted area (32% vs. 43%, respectively; p=0.10) when both AMI groups (Empty and BM-MNC) were compared. Also TNF-α and IL-6 levels showed no difference between all groups. We concluded that paracrine effects of cell-based therapy with BM-MNC was unable to modulate events associated to AMI in rat in spite of cell viability after 7 days of implantation.