Longevity Briefs: Using Electricity To Repair Damaged Tissue

Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

The problem:

Today, medical science mostly focuses on the chemical interactions within our bodies, searching for drugs that can leverage these reactions to improve health. However, our cells don’t just respond to chemicals, but also to physical stimuli like pressure, light and even electricity. Since before we had electricity running through our walls, scientists knew that the body contained electricity in some form, since pricking the skin would produce an electric current. This current comes from charged ions flooding across the damaged cell membrane, and seems to serve as a signal to initiate wound healing.

Several studies in both tissue culture and animal models now suggests that electric currents can be used to accelerate healing in various different contexts, from regular superficial wounds to nerve damage following surgery. In this study, researchers identify one potential mechanism for this effect, which involves a type of white blood cell called macrophages. Macrophages serve a dual purpose in wound healing. Early on, they promote inflammation at the site of the injury, which helps to hedge against any pathogens that might find their way into the wound. As time goes on, macrophages switch over to an anti-inflammatory ‘mode’ in which they promote tissue repair. Sometimes, however, this switch doesn’t happen, leading to persistent inflammation, slow healing and the formation of scar tissue instead of complete healing.

The discovery:

Researchers wanted to investigate how macrophages responded to electrical currents. They isolated human macrophages from the blood of healthy donors and exposed them to an alternating current for one hour at 2.5 volts and 1 hertz, which mimics natural bioelectric signals in the body. They found that the behaviour of these macrophages changed in comparison to those that were not stimulated: they developed “extended pseudopods” – arm-like extensions typically associated with the uptake of cellular debris, suggesting the macrophages had entered ‘cleanup mode’. They also began producing anti-inflammatory proteins associated with wound healing and blood vessel formation, and these effects lasted for up to 72 hours after just a single hour of stimulation.

To further confirm the anti-inflammatory effect, macrophages were electrically stimulated before being exposed to a strong inflammatory trigger called lipopolysaccharide (LPS), which is a component of the cell walls of some bacteria. The pre-treatment with electrical stimulation significantly reduced the expression of pro-inflammatory markers that would normally surge in response to LPS.

The implications:

This study suggests that electrical stimulation can reprogram macrophages to an anti-inflammatory, pro-regenerative state, and that this reprogramming lasts quite a long time compared to the duration of the stimulation. This could be very useful, for example, for treating certain wounds that are resistant to healing or promoting more successful recovery from surgery. There is already some human evidence that electrical currents may be used to accelerate wound healing, but there is a lot of work to be done in order to figure out exactly how electrical currents should be applied to achieve the best results.

There are also other contexts besides wound healing in which we might want to switch macrophages away from their inflammatory mode. In atherosclerosis for example, inflammatory macrophages within the fatty plaque are major drivers of plaque growth, while anti-inflammatory macrophages seem to be protective. Delivering electrical currents to these macrophages may not be possible, but further study might reveal the mechanisms through which electrical currents influence macrophage behaviour, pointing us in the direction of new drugs.