Abstract 8648: Human Macrophage Regulation via Interaction with Pericardial Adipose Tissue-Derived Mesenchymal Stromal Cells
Background: While mesenchymal stromal cells (MSCs) were found to improve tissue repair, their mechanism of action is not fully understood. We aimed to test the hypothesis that MSCs may act via macrophages and that specifically, human pericardial adipose tissue-derived MSCs can polarize human macrophages into reparative, anti-inflammatory (M2)-like phenotype.
Methods and Results: MSCs were isolated and expanded from pericardial adipose tissue of patients undergoing cardiac surgery. Monocytes isolated from human blood using Ficoll and MACS positive selection of CD14+ cells were cultured 5-7 days, washed, and co-cultured with MSCs 1-14 days directly or through a transwell membrane restricting cell contact. Supernatant was collected on different days for cytokine analysis by ELISA. M2 macrophage markers (CD206, CD163 and CD16) and phagocytic ability of fluorescent latex beads were examined using flow cytometry. We found that human MSCs increased the percentage of macrophages expressing alternative macrophage (M2) markers CD206+CD163+ (1.5 fold) and CD16+ (9 fold). MSCs also increased macrophage secretion of anti-inflammatory and reparative cytokines IL-10 (Fig; 9 fold, p<0.001), VEGF (3 fold, p<0.01), IL-13 (2 fold, p<0.05) and IL-4 (2 fold, P<0.05), and decreased IL-1 (2 fold, p<0.01), TNF-α (1.5 fold, p<0.001), IL-12 (1.5 fold, p<0.001), IL-17 (3 fold, p<0.001), IL-23 (16 fold, p<0.01) and IFN-γ (2 fold, p<0.001). In addition, co-culturing induced a star-shaped morphology of macrophages and decreased their phagocytic ability (2 fold).
Conclusions: Our findings suggest, for the first time, that human pericardial adipose tissue-derived MSCs can polarize human macrophages towards anti-inflammatory, reparative phenotype. Our findings could be relevant for the mechanism of atherosclerosis and the development of novel immune-modulation therapy for the treatment of MI, atherosclerosis and other inflammatory diseases.
- © 2011 by American Heart Association, Inc.