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Biological Chemistry

Biomaterials coax immune cells to help heal damaged tissue

Findings in mice could lead to therapies that regenerate tissue after injuries

by Michael Torrice
April 15, 2016

Two slices of mouse muscle tissue showing the difference in tissue renegeration.
Credit: Kenneth Estrellas/Johns Hopkins Medicine
Slices of quadriceps muscle tissue from mice lacking T cells, taken after researchers treated a wound with biomaterial suspensions. Mice injected with normal T cells regenerated muscle tissue (left), and animals getting cells unable to turn into type 2 helper T cells formed scar tissue (light purple, right).

When bioengineers develop materials for medical implants or scaffolds for tissue engineering, they often worry about the immune system. They look for ways to avoid sparking an immune response that could lead to inflammation and formation of scar tissue around the materials.

But a new study in Science suggests that intentionally triggering an immune response could sometimes be helpful. A team led by Jennifer H. Elisseeff of Johns Hopkins University showed that certain immune cells can promote healing in response to some biomaterials (Science 2016, DOI: 10.1126/science.aad9272). The findings could lead to biomaterial-based therapies that regenerate tissue after injuries or infections.

“It’s almost the opposite of what you’d expect,” says Stephen F. Badylak of the University of Pittsburgh, who wrote a commentary accompanying the new report. “They’re suggesting working with the immune system instead of fighting it.”

Elisseeff’s team studied wounds they created in the leg muscles of mice. The muscle tissue regenerated after the researchers injected materials derived from pig bone and muscle into the wounds. These materials consisted of colloidal suspensions of processed extracellular matrix, the protein and polysaccharide scaffolding that supports cells inside tissues.

After examining the immune response at the injury site, the researchers hypothesized that type 2 helper T cells might be crucial for the regeneration. These cells normally fight off parasitic worm infections and are involved in some allergic reactions.

To confirm these cells are needed for regeneration, the team made similar injuries in mice engineered to lack T cells. After treatment with the biomaterial suspensions, these animals did not regrow much muscle tissue and struggled in a treadmill test of muscle function.

When the researchers injected some of these engineered animals with normal T cells, they observed almost full functional recovery. But mice receiving injections of T cells incapable of becoming the type 2 helper form showed little improvement, indicating that activation of these cell types is necessary for regeneration.

The researchers think that these helper T cells release signaling molecules that recruit other immune cells called macrophages to clear out dead cells and control the local inflammatory response.

“We can now use this information to try to induce this pathway with new biomaterials development,” Elisseeff says. One method, she says, could involve pairing biomaterials with small molecules that activate type 2 helper T cells.

Badylak also thinks the findings will prompt researchers to look more closely at the immune response to biomaterials to try to find other cell types that promote regeneration.

A lot of work on tissue regeneration has focused on stem cells and formation of blood vessels, Elisseeff says, but researchers should also consider the immune system. “The immune system is the first responder to a foreign body,” she says. “Maybe it’s this response that is dictating what is happening later on with stem cells and vascularization.”



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