Mesenchymal stem cells from gum tissue accelerate wound healing Perhaps no surprise that wound healing process in the mouth is much faster than one in the skin. Gum tissue regeneration is about two times faster, and moreover the scar formation in gums is reduced. A study, published in Science Translational Medicine, demonstrated that gingival mesenchymal stem cells (GMSCs) could be one of the main reasons of this accelerated healing.
Adult skin wound healing can be regulated by numerous secreted factors including cytokines, growth factors, chemokines, and extracellular vesicles. Mesenchymal stem cells (MSCs) are capable of self-renewal and differentiation into mesenchymal and non-mesenchymal lineages, they have been used in therapy for tissue regeneration and autoimmune disease treatment. MSC-derived exosomes reduce apoptosis and promote collagen synthesis and angiogenesis therefore providing cutaneous wound healing. Compared to adults, fetal wounds heal faster, almost scarless and display only mild inflammation. Like fetal wounds, oral gingival/mucosal wounds heal faster than cutaneous wounds and exhibit minimal scar formation, which may be due to reduced inflammatory cell infiltration and proinflammatory factor production in the gingiva.
In 2009 a group of scientists from Penn Dental Medicine discovered that the gingiva contains mesenchymal stem cells releasing lots of signaling molecules in extracellular vesicles as all the MSCs do. However, it was unknown whether GMSCs have a specific secretory mechanism to regulate wound healing in the gingiva.
To understand what distinguishes mesenchymal stem cells in the gingiva from those in the skin, the research team ran a study in 2018. Songtao Shi, chair and professor of Penn Dental Medicine's Department of Anatomy and Cell Biology , was the senior author on the study. Xiaoxing Kou, a visiting scholar at Penn Dental Medicine, was the first author on the work. They collaborated with colleagues from the Peking University, the University of Southern California, the Children's Hospital of Philadelphia, and the National Institute of Dental and Craniofacial Research.
They found that the GMSCs contained more proteins overall, including the inflammation-dampening IL-1RA, which blocks a proinflammatory cytokine. IL-1RA also used as a therapy to treat rheumatoid arthrisits, an inflammatory condition.
Around the margins of wounds, they found IL-1RA was increased in GMSCs, while mice lacking IL-1RA took longer to heal gingival wounds. In contrast, when the researchers isolated IL-1RA secreted from GMSCs and injected it into wounds, it significantly accelerated healing.
"Our paper is just part of the mechanism of how these stem cells affect wound healing," 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, including the delayed wound healing seen in diabetic patients." Moving forward, Shi, Kou and colleagues want to move their work into the clinic."We are targeting translational therapies," says Shi. "These cells are easy to harvest from the gingiva, and that makes them a beautiful cell for clinical use. We have a lot of work ahead of us, but I can see using these cells to reduce scar formation, improve wound healing, and even treat many inflammatory and autoimmune diseases."