Gum tissue repairs itself roughly twice as fast as skin and with reduced scar formation. Researchers at the School of Dental Medicine set out to determine whether and how gingival mesenchymal stem cells (GMSCs) play a role in accelerated wound healing.
Xiaoxing Kou, a visiting scholar at Penn Dental Medicine, was the first author on the work. Dr. Kou and Songtao Shi, chair and professor of Penn Dental Medicine’s department of anatomy and cell biology and the study’s senior author, collaborated with colleagues Chider Chen and Anh Le from Penn Dental Medicine as well as Yanheng Zhou from Peking University, Xingtian Xu from the University of Southern California, Los Angeles, Claudio Giraudo and Maria L. Sanmillan from the Children’s Hospital of Philadelphia and Tao Cai from the National Institute of Dental and Craniofacial Research.
From earlier work by Dr. Shi’s group and others, it was clear that mesenchymal stem cells perform many of their functions by releasing signaling molecules in extracellular vesicles. Comparing these extracellular vesicles in the skin and the gingiva, they found that the GMSCs contained more proteins, including the inflammation-dampening IL-1RA, which blocks the proinflammatory cytokine.
They examined wound tissue and found IL-1RA was increased in GMSCs around margins of wounds. Mice lacking IL-1RA, or in which it was inhibited, took longer to heal gingival wounds. In contrast, when the researchers isolated IL-1RA that had been secreted from GMSCs and injected it into wounds, it significantly accelerated wound healing.
“We found that mesenchymal stem cells, and especially gingival mesenchymal stem cells, release large amount of cytokines through an extracellular vesicle,” says Dr. Kou.
These findings may have special significance for people with diabetes. The researchers found that GMSCs in mice with diabetes were less able to secrete extracellular vesicles compared to GMSCs in healthy mice, and their GMSCs also had less IL-1RA secretion. Introducing extracellular vesicles secreted from the GMSCs of healthy mice reduced wound healing time in diabetic mice.
“Our paper is just part of the mechanism of how these stem cells affect wound healing,” Dr. Kou says, “but I think we can build on this and use these cells or the extracellular vesicles to target a lot of different diseases.”