Mononuclear cells promote mesenchymal stem cell migration after myocardial infarction / 中国组织工程研究

ABSTRACT

BACKGROUND:The mechanisms of mesenchymal stem cells directional y homing to infarcted myocardium post myocardial infarction are stil unclear. OBJECTIVE:To investigate the role of stromal cellderived factor-1 (SDF-1)/C-X-C chemokine receptor 4 (CXCR4) axis on mesenchymal stem cellmigration promoted by mononuclear cells after myocardial infarction. METHODS:Cardiomyocytes and mesenchymal stem cells were respectively isolated from suckling and adult Sprague-Dawley rats. Twelve healthy Sprague-Dawley rats were selected (six rats for myocardial infarction models and six for sham models), then circulating mononuclear cells were isolated. 4,6-Diamino-2-phenyl indole-labeled mesenchymal stem cells, cardiomyocytes and mononuclear cells were cultured into the upper, middle and lower layers of the tri-chamber coculture system, respectively. In this experiment, there were four groupsmyocardial infarction group, AMD3100 (CXCR4 inhibitor) group, sham group and blank control group. After 48 hours, the number of migrating mesenchymal stem cells with blue-lighting nucleus was calculated under fluoroscope. Immunocytochemistry and immunofluorescent staining was used to detect SDF-1 expression in cardiomyocytes and CXCR4 expression in mesenchymal stem cells, respectively. RESULTS AND CONCLUSION:Migrating mesenchymal stem cells with positive expression of CXCR4 were observed in each group other than the blank control group. The number of migrating mesenchymal stem cells was higher in the myocardial infarction group than in the other groups. Tumor necrosis factor-αneutralizing antibody and CXCR4 inhibitor AMD3100 could obviously reduce the number of migrating mesenchymal stem cells (P<0.05). Cardiomyocytes in each group expressed SDF-1 positively. The gray values of SDF-1 expression in the myocardial infarction and AMD3100 groups were significantly higher than those in the sham and blank control groups (P<0.05). SDF-1/CXCR4 axis plays a certain role in mesenchymal stem cells migration promoted by mononuclear cells after myocardial infarction.