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Newly identified oral stem cell key to wound healing

Researchers found that the roof of the mouth is home to a unique type of stem cell (green), which normally is not actively dividing (top panel). In response to wounding, these cells begin dividing (red) and move toward the site of injury to the right (bottom panel).Byrd et al., Cell Stem Cell

When you get a cut or sore inside your mouth, you may notice it’s already getting better by the next day. Studies have confirmed that the mouth heals faster than the skin. Researchers have been studying oral stem cells to try to understand how the mouth rapidly recovers from injury, even in the face of constant challenges from chewing and exposure to microbes.

Stem cells live in many types of adult tissues, including the lining inside the mouth, called the oral epithelium. These oral stem cells can divide throughout life to replenish other cells that become damaged or diseased.

A team led by Drs. Kevin Byrd and Scott Williams of the University of North Carolina at Chapel Hill examined stem cells in the oral epithelium under normal conditions and in response to stress. The research was supported by NIH’s National Institute of Dental and Craniofacial Research (NIDCR), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and National Cancer Institute (NCI). Results were published in Cell Stem Cell on December 5, 2019.

The scientists labeled and tracked oral epithelial stem cells in mice and compared cell behaviors across different tissues in the mouth. The experiments revealed a new type of stem cell in the roof of the mouth, the hard palate. These so-called “slow-cycling” cells divide infrequently and reside in specific areas on the ridges of the hard palate.

Next, the scientists examined the stem cells’ reactions to different levels of physical stress. In response to a small puncture wound in the hard palate of mice, the slow-cycling cells began rapidly dividing and migrated into the injury to renew the tissue. Feeding mice soft food (compared to a normal hard-pellet diet) evoked an opposite reaction: the stem cells divided less frequently.

By analyzing the cells’ RNA sequences, the scientists identified a gene, Lrig1, which showed high activity, or expression, in the slow-cycling stem cells. LRIG1 expression decreased near wounds in the hard palate and increased in response to a soft diet. These findings suggest that LRIG1 plays an important role in keeping the cells dividing slowly under low-stress conditions. As further evidence, mice genetically engineered to lack Lrig1 had increased stem cell division.

“Overall, the results indicate that oral epithelial stem cells in the hard palate are sensitive to both genes and the environment, responding quickly to daily challenges such as eating and to higher-stress events like injury,” Byrd says. “This knowledge could help scientists better understand how we get oral cancer, which is rare in the hard palate. It could also inform efforts to improve wound healing and tissue repair throughout the body.”

—by Catherine Evans, Ph.D.