Electromodulation Immune Therapy

by Ghost a minute ago 4 min read

Electrical Stimulation Reprograms Macrophages to Promote Tissue Repair and Reduce Inflammation

New research from Trinity College Dublin suggests that applying electrical stimulation to human macrophages—key immune cells involved in fighting infection and orchestrating healing—can shift them toward an anti-inflammatory, regenerative state. This modulation impedes excessive inflammation while enhancing processes like angiogenesis and cell migration, offering encouraging insights into new potential therapies.

The Role of Macrophages in the Immune System

Macrophages, a type of white blood cell, serve multiple roles in the immune system. They clear debris, combat pathogens, and signal other cells to aid in tissue repair. However, when their inflammatory response persists unchecked, it can contribute to chronic conditions, underscoring the need for strategies to regulate their behavior for better health outcomes.

Study Design and Methodology

In the study, published in Cell Reports Physical Science, researchers at Trinity College Dublin isolated macrophages from healthy donor blood and applied electrical stimulation using a custom bioreactor. The regime involved a biphasic pulse of ±2.5 V at 1 Hz for 1 hour, a setup designed to mimic natural bioelectric signals without harming the cells.

Insights from the Researchers

“We have known for a very long time that the immune system is vital for repairing damage in our body and that macrophages play a central role in fighting infection and guiding tissue repair,” said Dr Sinead O’Rourke, Research Fellow in Trinity’s School of Biochemistry and Immunology, and first author of the research article.

“As a result, many scientists are exploring ways to ‘reprogramme’ macrophages to encourage faster, more effective healing in disease and to limit the unwanted side-effects that come with overly aggressive inflammation. And while there is growing evidence that electrical stimulation may help control how different cells behave during wound healing, very little was known about how it affects human macrophages prior to this work.”

“We are really excited by the findings. Not only does this study show for the first time that electrical stimulation can shift human macrophages to suppress inflammation, we have also demonstrated increased ability of macrophages to repair tissue, supporting electrical stimulation as an exciting new therapy to boost the body’s own repair processes in a huge range of different injury and disease situations.”

Key Results

Results indicated that stimulated macrophages exhibited enhanced viability, phagocytosis (the process of engulfing debris), and expression of gap junction protein Connexin 43, which aids cell communication. They also showed elevated levels of anti-inflammatory markers like CD163 and CD206, alongside reduced responses to inflammatory triggers such as lipopolysaccharide (LPS). Furthermore, these cells promoted angiogenic tube formation in endothelial cells and migration of mesenchymal stem cells in a wound scratch model, effects that persisted up to 72 hours post-stimulation.

Electromodulation of human monocyte-derived macrophages drives a ... — (A) Untreated (Mø) or LPS-treated (100 ng/mL, 24 h) primary human macrophages were plated in the custom bioreactor (2 × 10⁶ cells/well) and stimulated with electrical stimulation (±2.5 V, 1 Hz, 2 ms) for 1 h. Following stimulation, the cells were left to rest or else previous Mø cells were further stimulated with LPS (100 ng/mL) for 24 or 72 h. At 24 or 72 h, macrophage phenotype was characterized. Gene expression was assessed by real-time PCR. Protein expression was assessed by flow cytometry and western blot. Cytokine production was assessed by ELISA.(B) Image shows (i) bioreactor plate connected to breadboard, (ii) signal generator, and (iii) oscilloscope.(C) Graph showing electrical stimulation regime, showing frequency, amplitude, and wave shape applied to macrophages.

Significance of the Findings

The findings from the interdisciplinary team led by Trinity investigators, Professor Aisling Dunne (School of Biochemistry and Immunology) and Professor Michael Monaghan (School of Engineering) are especially significant given that this work was performed with human blood cells (showing its effectiveness for real patients); electrical stimulation is relatively safe and easy in the scheme of therapeutic options; and the outcomes should be applicable to a wide range of scenarios.

Future Directions

Corresponding author Prof. Monaghan added: “Among the future steps are to explore more advanced regimes of electrical stimulation to generate more precise and prolonged effects on inflammatory cells and to explore new materials and modalities of delivering electric fields. This concept has yielded compelling effects in vitro and has huge potential in a wide range of inflammatory diseases.”