Human macrophage regulation via interaction with cardiac adipose tissue-derived mesenchymal stromal cells.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Mesenchymal stromal cells (MSCs) improve tissue repair but their mechanism of action is not fully understood. We aimed to test the hypothesis that MSCs may act via macrophages, and that specifically, human cardiac adipose tissue-derived mesenchymal stromal cells (AT-MSCs) can polarize human macrophages into a reparative, anti-inflammatory (M2) phenotype. Methods and We isolated and grew AT-MSCs from human cardiac adipose tissue obtained during cardiac surgery. Macrophages were grown from CD14(+) monocytes from healthy donor blood and then cocultured with AT-MSCs, with and without transwell membrane, for 1 to 14 days. In response to AT-MSCs, macrophages acquired a star-shaped morphology, typical of alternatively activated phenotype (M2), and increased the expression of M2 markers CD206(+), CD163(+), and CD16(+) by 1.5- and 9-fold. Significantly, AT-MSCs modified macrophage cytokine secretion and increased the secretion of anti-inflammatory and angiogenic cytokines: interleukin (IL)-10 (9-fold) and vascular endothelial growth factors (3-fold). Moreover, AT-MSCs decreased macrophage secretion of inflammatory cytokines such as IL-1α (2-fold), tumor necrosis factor α (1.5-fold), IL-17 (3-fold), and interferon gamma (2-fold). Remarkably, the interaction between AT-MSCs and macrophages was bidirectional and macrophages enhanced AT-MSC secretion of typical M2 inducers IL-4 and IL-13. N

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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