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Study Shows Key to Improved Healing for Wounds

Posted on March 31, 2018


A study conducted by researchers at the University of Pennsylvania aims to answer the commonly asked question of why injuries inside the mouth heal much faster than injuries to the skin, and often without scars.

Their answer? Stem cells.

Specifically, gingival mesenchymal stem cells, or stem cells in the gum tissues. Stem cells are basic, primitive cells with the ability to develop into many different types of cells and tissues.

The study findings were published in Science Translational Magazine and combine theories and findings from several research projects conducted by the university regarding how the mouth heals.

The research was performed by scholars at the Penn Dental Medicine’s Department of Anatomy and Cell Biology along with individuals from Peking University, UCLA, the Children’s Hospital of Philadelphia and the National Institute of Dental and Craniofacial Research.

In 2009, the Penn dental school discovered that gum tissue contained mesenchymal stem cells, and these cells had the powerful ability to heal mouth injuries. The researchers also discovered that these mesenchymal stem cells discharge a large amount of proteins, but they were unsure at the time how these proteins sped up healing in the mouth.

The first part of the project was to understand how the mesenchymal stem cells in the gum tissues are different from those found in the skin. To do so, the Penn team looked at the extracellular vesicles of the cells. Extracellular vesicles are membrane-bound structures released by cells that are believed to have diagnostic and therapeutic benefits.

Some types of extracellular vesicles include exosomes, microvesicle and apoptotic bodies, vesicles that help to manage the communication between cells during normal function and during illness.

During their examination, the study authors found that the gingival mesenchymal stem cells have more proteins than the mesenchymal stem cells of the skin, including the protein IL-1RA, which reduces inflammation by blocking a pro-inflammatory cytokine.

Cytokines are substances such as interferon and growth factors released by the immune system that affect other cells.

The IL-1RA protein is also used to treat individuals living with rheumatoid arthritis, an autoimmune condition that causes inflammation of the joints and other tissues.

After measuring the number of proteins released by the gingival mesenchymal stem cells and the skin stem cells, the researchers took a longer look to determine what part of the cells manage the emission of the IL-1RA and other cytokines and found that the GMSCs had higher levels of the protein Fas compared to the skin mesenchymal stem cells. The researchers believe that Fas helps in managing regulation of the immune system.

The researchers also found that mice with lower amounts of Fas had lower amounts of IL-1RA. These mice also had reduced secretion of IL-1RA in response to injury.

Delving deeper into the cells, the researchers also found that Fas combined with two other proteins, Fap-1 and Cav-1, that sparks the release of small extracellular vesicles.

To connect how the increased number of proteins and extracellular vesicles increase the speed of healing, the researchers examined wound tissue and found that IL-1RA was increased in the GMSCs found in the edges of wounds. Mice that lacked IL-1RA or in which the protein secretion was repressed had gingival wounds that took longer to heal.

The researchers then took isolated IL-1RA released by the GMSCs and injected it into the slow-to-heal gingival wounds, and found it significantly sped up wound healing.

The findings have further benefits to the body beyond the mouth.

“Diabetes affects the ability of wounds to heal, which leaves patients at risk for complications such as infection,” said Dr. Joel Singer, a New York physician who practices regenerative medicine.

During the Penn study, the researchers connected their study to the treatment of wounds that were slow to heal because of diabetes. They found that the extracellular vesicles taken from the GMSCs of healthy mice improved healing times in mice with diabetes.

“The ability to speed up healing of wounds would be of significant benefit to individuals living with diabetes,” Singer said.


University of Pennsylvania. “Unraveling how mesenchymal stem cells from gum tissue accelerate wound healing.” ScienceDaily. ScienceDaily, 14 March 2018.


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