Why do some applications of electric fields appear to enhance regeneration from injury? The study of the effects of electromagnetism on cell behavior lags far behind the study of biochemistry, the effects of proteins and small molecules. Here, researchers provide evidence for electrical stimulation to be able to shift macrophage cells into a more pro-regenerative state. Macrophages are innate immune cells resident in tissue that conduct a wide range of tasks relating to defense against pathogens, destruction of harmful cells, and coordination of tissue maintenance. Macrophages adopt packages of behaviors dependent on circumstances; the most prominent model for describing those behaviors is the distinction between M1 macrophages (aggressive, inflammatory) and M2 macrophages (regenerative, anti-inflammatory). A fair amount of research effort has been directed towards ways to encourage macrophages to adopt a specific desired state in order to treat disease, particularly inflammatory disease.
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.
Link: https://doi.org/10.1016/j.xcrp.2025.102795
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