Hundreds of thousands of people suffer from burn injuries every year and it’s a leading cause of morbidity worldwide. While minor burns can be treated at home, much more severe burns can require surgery, often leaving patients with scars, disabilities and disfigurement that can result in stigma. Regenerative medicine could dramatically improve how victims heal from wounds and researchers have just identified a novel pathway in cells that brings us one step closer to realizing its full potential.
This cell-signaling pathway can regenerate hair follicles and skin while healing from the wounds. Drugs that target this pathway could decrease scarring and transform how wounds heal. Researchers detail their exciting discovery in the journal Cell Stem Cell.
“A lot of people don’t realize that you have hair follicles all over your body – even places you don’t see hair,” senior author Luis Garza, associate professor of dermatology at the Johns Hopkins University School of Medicine, tells IFLScience.
“So if you look at your face, all the pores you see on your skin are actually pores for tiny hair follicles. And the presence of hair follicles is what makes normal and scarred skin look different.”
Researchers first looked at two groups of mice, where one was quite good at regenerating skin and hair follicles after wounds and the other was not able to do this. When comparing gene expression in healed wounds, researchers identified the particular pathway involved in regeneration.
They found that the protein known as toll-like receptor 3 (TLR3) is particularly important in promoting skin and hair follicle regeneration. This protein is a receptor that binds to a substance called double stranded RNA (dsRNA), which signals damage and triggers an immune response. TLR3 then switches on two genes, IL6 and STAT3, to enhance regeneration during wound healing. TLR3 also activates other molecules involved in hair development and the gene EDAR, which makes a protein – ectodysplasin – that's important for skin development. Researchers found that the expression of TLR3 was three times higher in the group of mice who were good at regeneration, compared to the control group.
“Our paper is basically proving through a series of tests that if we turn on this pathway good regeneration happens, and if we turn it off we don’t get regeneration. What we want to do with these findings is test whether we can create new hair follicles in lots of different contexts that we think will benefit people,” Garza says.
Researchers also looked at the expression of TLR3 in scratched and healthy human skin cell samples. They found that the expression of TLR3 was five times higher in the scratched skin cell samples. In another set of experiments, researchers found that adding synthetic dsRNA to mouse skin wounds dramatically increased the number of regenerative follicles, while disrupting dsRNA decreased the amount of regenerative follicles.
He explains that the hair follicle is the anchor for a lot of blood vessels, nerves and stem cells to become invested in the skin. Garza and his research team suggest that if we can make new hair follicles, we can better attract all of these secondary structures that help remodel and add function to the new skin. This would help burns to look and act more like healthy skin.
Garza and his research are now working alongside drug companies to identify and develop compounds that activate TLR3 and enhance regeneration. They do caution that this process will take many more years before we see clinical application, but are “excited” about the potential of this pathway.