Their focus was on macrophages, immune cells with a unique ability to switch between two different states. As well as directing the immune response, macrophages are secretory cells, meaning they actively release molecules and particles that communicate with surrounding cells to coordinate repair. When a bone breaks, macrophages rush to the site and drive an inflammatory response, clearing up damage such as dead cells and bone fragments. These are called M1 macrophages. Once that job is done, macrophages switch to a second state, called M2, which helps reorganise and rebuild the bone. How exactly this switch was influencing bone repair was still poorly understood. This study has gone some way to solving that puzzle. It is known that macrophages release tiny particles called extracellular vesicles, which pinch off from the cell surface and are taken up by neighbouring cells. What this group discovered was the specific role these extracellular vesicles play in bone repair, and crucially, that their effects depend entirely on which state the macrophage is in when it releases them. M1 macrophage extracellular vesicles were found to kickstart new bone formation, while M2 macrophage extracellular vesicles promoted the growth of new blood vessels, a process essential for delivering nutrients to the healing site.
Creating a New “Hybrid” Healing Signal
Another important aspect of this study was metabolism, which refers to all the chemical reactions that keep our cells working. The team found that the metabolic state of a macrophage directly shapes which type of particles it releases. Using a drug called DASA-58, they were able to shift M1 macrophages into a new hybrid state, somewhere between M1 and M2, and found that the particles released by these hybrid cells reflected that change. These hybrid particles were able to both support new bone formation and promote blood vessel growth at the same time, effectively combining the benefits of both M1 and M2 particles into a single population, without triggering unwanted inflammation.
Why This Matters
Slow or impaired bone healing is common in older adults, people with diabetes, and patients with large or complex fractures. This research suggests a new way to create cell derived therapies that could speed up recovery and improve outcomes.
Lead author Dr. Cansu Gorgun said:
“We’ve shown that it’s possible to guide immune cells to produce vesicles that support multiple stages of healing. This could be a valuable approach for improving bone repair.”
Senior authors Prof. David Hoey and Prof. Annie Curtis added:
“By reprogramming cell metabolism, we can design new kinds of regenerative signals. This is a promising step toward next generation therapies for patients.”
Funding
This project is funded by the European Union under Marie Sklodowska- Curie Post-doctoral Fellowship and by Research Ireland through the Frontiers for the Future Project Grant.
For more information, please contact:
Prof. David Hoey – dahoey@tcd.ie
Prof. Annie Curtis – anniecurtis@rcsi.ie