A macrophage (green and blue) sports a backpack (red) attached to its surface, which is delivering anti-inflammatory signals to keep the cell in a healing state. Credit: Wyss Institute at Harvard University
Key points:
- Researchers developed a new approach for treating traumatic brain injury (TBI) that leverages macrophages—a type of white blood cell that can dial inflammation up or down.
- The team created disc-shaped microparticles called “backpacks” that contain two anti-inflammatory molecules and attached them to macrophages in pig models of TBI.
- Pigs that received macrophage treatment had lesions that were 56% smaller and showed significantly less hemorrhaging and inflammation than untreated animals.
New research, published in PNAS Nexus, details an approach for treating traumatic brain injury (TBI) that leverages macrophages—a malleable type of white blood cell that can dial inflammation up or down in response to infection and injury.
Runaway inflammatory cascades in the brain can cause TBI damage. As cells die from impact, they release pro-inflammatory cytokines that attract immune cells to clean up the damage. At the same time, cytokines disrupt the blood-brain-barrier causing blood to leak into the brain and trigger swelling, impaired oxygen delivery, increased inflammation, and further cell death.
In the current study, researchers created disc-shaped microparticles nicknamed “backpacks” that contain two anti-inflammatory molecules—dexamethasone and interleukin-4. They incubated the microparticles with both human and pig macrophages and saw that the backpacks stably stuck to macrophages. The technique also kept macrophages in a healing state as expression of pro-inflammatory biomarkers decreased and expression of anti-inflammatory biomarkers increased.
Researchers then used pigs as a model organism to validate the backpack approach. They infused backpack-wearing porcine macrophages into the pigs’ bloodstream four hours after a TBI and analyzed their brains seven days later. Pigs that received macrophage treatment had lesions that were 56% smaller and showed significantly less hemorrhaging than untreated animals. Macrophages likely accomplished their damage control by reducing brain inflammation as evidenced by a lower level of biomarkers for inflammation in treated animals relative to untreated animals.
Looking ahead, the team plans to determine how anti-inflammatory macrophage therapy affects the blood-brain barrier’s integrity to prevent bleeding. This discovery would provide insight into treating other conditions like hemorrhagic stroke.
“This impressive study describes a truly novel and potentially powerful macrophage-based therapy for treating the inflammation that is the root cause of so many human afflictions in an effective and non-invasive way that works with biology rather than against it,” said Donald Ingber, professor at Harvard University.