Electromodulation of human monocyte-derived macrophages drives a regenerative phenotype and impedes inflammation

Modulation of the immune response, in particular innate immune cells such as macrophages, has emerged as a promising strategy to combat degenerative disease and promote effective tissue repair. Electrical stimulation has the potential to regulate cell function during wound healing and regeneration; however, studies to date regarding the effects of electrical stimulation on macrophages remain limited, particularly regarding primary human cells. Here, we demonstrate that electrical stimulation exhibits an immunomodulatory effect on primary human macrophages, promoting an anti-inflammatory pro-regenerative phenotype, accompanied by decreased inflammatory macrophage marker expression and enhanced expression of angiogenic genes. Furthermore, we highlight the ability of electrically stimulated macrophages to promote angiogenic tube formation in human umbilical vein endothelial cells (HUVECs), as well as mesenchymal stem cell (MSC) migration in a wound scratch model. Collectively, these findings endorse electrical stimulation as a viable therapeutic strategy for the modulation of macrophages across multiple injury and defense microenvironments.