Macrophages can be altered to support and speed the regeneration of peripheral nerves in mice following injury, Johns Hopkins Medicine researchers have found. The nerves outside the brain and spinal cord, known as peripheral nerves, have the capacity for regeneration, but the rate of natural renewal is so slow that many nerve injuries lead to incomplete recovery and permanent disability for patients.
Brett Morrison M.D., Ph.D., associate professor of neurology at the Johns Hopkins University School of Medicine; Mithilesh Kumar Jha, Ph.D., postdoctoral research fellow at Johns Hopkins; and colleagues used genetic manipulations on the macrophages in mice to investigated whether altering the metabolism of macrophages would impact the recovery from nerve injury.
In a recently published paper1, the researchers determined that removing a specific metabolic transporter (a protein that facilitates movement of metabolites across membranes) — monocarboxylate transporter 1 (MCT1) — delayed recovery from nerve injury.
This was accompanied by alterations in several macrophage cellular functions, including the ability to collect foreign or dead cells, and to secrete specific cytokines (proteins produced by cells in the immune system) that communicate with other immune cells to coordinate the immune system’s overall response to injury.
Of even greater clinical interest, say the researchers, was their discovery that increasing MCT1 in macrophages led to improved recovery following nerve injury in mice.
It was surprising how effective it was. We were able to accelerate the recovery from nerve injury by increasing MCT1. This opens up new avenues for potentially treating severe nerve injuries that can occur from traumas such as a motor vehicle accident or gunshot wounds.
According to Jha, another exciting advance from the study was the demonstration that macrophages that were purified outside the body and intravenously injected into mice could impact nerve recovery.
This finding could lead to a treatment for peripheral nerve injuries—for which no medical therapy currently exists—where a person could receive an injection of their own macrophages with upregulated levels [higher amounts from increased production] of MCT1,
Mithilesh Kumar Jha et al. Macrophage monocarboxylate transporter 1 promotes peripheral nerve regeneration after injury in mice. Journal of Clinical Investigation (2021).DOI: 10.1172/JCI141964 ↩︎