CXCR4+ and SDF-1+ Bone Marrow Cells Are Mobilized into the Blood Stream in Acute Myocardial Infarction and Acute Ischemia

Abstract

Cell therapy has shown beneficial effects on ventricular function and tissue regeneration in patients with acute and chronic myocardial infarction, although with diverse grades of variability in the results, possibly by proportion, subtype and cell cycle status. Objective: Identify and phenotypically characterize, via CXCR4 and SDF-1 expression, the bone marrow cell subpopulations that are mobilized into the bloodstream in patients with Acute Myocardial Infarction (AMI) and Acute Ischemia (AI) such as acute angina and Chronic Ischemia (CI) such as chronic stable angina, and also determine the cell cycle status of these cells. Method: Patients with AMI and AI were recruited in the ICCU, and patients with CI in the departments of cardiology and cardiovascular surgery. The quantification of cellular subpopulations was made by cytofluorometry with a FACS caliburcyto fluorometry (Becton Dickinson) with specific FITC-labeled anti human monoclonal antibodies against CD34, CD133, CD117, CD48, CXCR4, SDF-1 and Ki67 (Becton Dickinson). Serum concentration of IL-6 and IL-8 were determined by a sequential solid phase chemiluminescent assay performed in a SIEMENS IMMULITE 1000 Analyzer. Statistical analysis was made with the SPSS version 20.0 for Windows. A p value 3/ml) than that in AI (9.2 ± 1.3 × 103/ml) and CI (6.6 ± 1.1 × 103/ml) patients (p p = 0.22 to 0.39), but interestingly in AMI and AI patients, cells were CXCR4+ in almost half of these mobilized cells, although the proportion was significantly higher in AMI patients (46.8% ± 7.1% to 55.7% ± 6.3% vs 23% ± 1.6% to 28.4% ± 2.1%, p = 0.03 to 0.05). A similar behavior was observed with the Ki67 antibody (29.9% ± 2.1% to 36.1% ± 6.3% vs 10% ± 1.2% to 24% ± 1.1%, p = 0.001 to 0.05). Bivariate analysis of the results showed a significant correlation of the cell proportion in AMI but not in AI and CI patients (p = 0.001 to 0.05; 0.12 to 0.87 and 0.17 to 0.92 respectively). The amount of myocardial tissue infarcted did not show any correlation with the amount of cellular subpopulations mobilized to peripheral blood (r = 0.10 to 0.20; p = 0.21 to 0.64) from the bone marrow. Conclusion: The proportion of cellular subpopulations with regenerative potential mobilized to circulation during an event of Acute Myocardial Infarction is significantly higher than during an event of acute angina and chronic stable angina, with a significant proportion of mobilized cells that expressed CXCR4, most of which were already in some of the cell cycle phases.