Abstract 16882: Temporal Changes in the Peripheral Blood Mononuclear Cell Populations After Acute Myocardial Infarction and Prediction of Improvement in Left Ventricular Function in the Cardiovascular Cell Therapy Research Network (CCTRN) TIME and Late-TIME Trials

Abstract

Background: Despite many cell-mediated attempts to promote myocardial repair after myocardial infarction (MI), no cell treatments are currently available. Instead, cell therapy clinical results remain mixed. We hypothesized that by evaluating changes in circulating cells in improvers and non-improvers in an MI cell therapy study, we could identify cells associated with repair that might be candidates for future cell therapy studies. Methods: In this study, peripheral blood (PB) was evaluated by flow cytometry at baseline and days 1, 30, 90 and 180 after bone marrow mononuclear cell (BMMNC) or placebo therapy from 207 consented patients in the CCTRN TIME (n=120) and Late-TIME (n=87) studies. A linear mixed model was used to determine changes over time in cell frequency. Multiple regression and discriminatory analyses were used to identify if changes in circulating cells predict changes in left ventricular ejection fraction (LVEF). Results: Changes in circulating cells were observed independent of treatment group. In TIME, a progressive decrease of CD11b+ cells started at day 30 (91.69±4.57 vs. 93.23±3.97%, p<0.05) and CD14+ cells began at day 90 (73.53±10.82 vs. 79.17±10.97%, p<0.05) compared to baseline. In Late-TIME, there was an increase in CD11b+ (94.01±3.82 vs. 92.81±3.98%, p<0.05) and CD14+ (81.70±6.64 vs. 77.94±9.29%, p<0.05) cells at day 1 when compared to baseline followed by a progressive decrease in the follow-up visits. A progressive decline in CXCR4+ cells started at day 30 in TIME (35.39 ±14.81 vs. 42.86±13.83%, p<0.05) and at day 1 in Late-TIME (42.81±14.33 vs. 47.74±15.13%, p<0.05). In TIME, a decrease of CXCR4+ cells at day 90 was a negative predictor of changes in LVEF from baseline to six months. Conclusion: Although multiple cell frequencies changed after treatment, only one cell frequency predicted changes in LVEF from baseline to six months. A significant reduction in CXCR4+ circulatory cells at day 90 after treatment is associated with improvement in LVEF. Further studies will be necessary to confirm the changes in circulatory cells and its impact on the regenerative capacity of patients with AMI.