Research teams at INSERM and Paris Descartes University have isolated dental stem cell lines and detailed the natural mechanism by which such cells repair lesions in teeth. This discovery could provide the foundation for therapeutic strategies that mobilize resident dental stem cells and amplify their intrinsic capacity for repair.
Teeth are mineralized organs that are anchored within the gums by roots. The outermost layer of the tooth is the enamel, which is one of the hardest substances in the body. Beneath the enamel is the dentine (sometimes known as the ivory), and the dentin (dentine if you are British) is filled with microscopic tubes that radiate from the inner pulp to the surface. These dentinal tubules contain cells called odontoblasts, which are the cells that made the dentin in the first place, and dentinal fluid (contains a mixture of albumin, transferrin, tenascin and proteoglycans). The odontoblasts maintain the dentin, but as we age, the dentin tubules calcify. Dentin is a yellowish, bone-like matrix that is porous. It is softer than enamel and decays more rapidly and is subject to severe cavities if not properly treated. Beneath the dentin is the pulp, which contains blood vessels and nerves and also houses a resident stem cell population.
When a dental lesion appears, the dormant stem cells in the pulp awaken and try to repair the tooth, but the means by which these cells do this is unknown.
To address these gaps in our knowledge, researchers from INSERM (French Institute of Health and Medical Research or Institut national de la santé et de la recherche), and the Paris Descartes University have extracted and isolated dental stem cells from the pulp of mouse molars and analyzed them further.
In the midst of their characterization of these cells, the French teams discovered that these dental pulp stem cells possess five different cell surface receptors for the neurotransmitters dopamine and serotonin. The present of these receptors suggested that the response of dental pulp stem cells to tooth injury was mediated by these neurotransmitters. Blood platelets, for example, are activated by binding serotonin and dopamine. Could these dental be activated by similar means?
The first set of experiments examined tooth repair in mice that lacked platelets that produced serotonin or dopamine. Such mice failed to repair tooth lesions, suggesting that serotonin and dopamine are important to inducing stem cell-mediated tooth repair.
Next, these laboratories characterized these five receptors and found that four of them were intimately involved in tooth repair; knocking out any one of the would abrogate tooth repair responses.
“In stem cell research, it is unusual to be simultaneously able to isolate cell lines, identify the markers that allow them to be recognized (here the receptors), discover the signal that recruits them (serotonin and dopamine), and discover the source of that signal (blood platelets). In this work, we have been able, unexpectedly, to explore the entire mechanism,” said Odile Kellermann, the principal author of this work.
Dentists use pulp capping materials like calcium hydroxide and tricalcium phosphate-based biomaterials to repair the tooth and fill lesions. These new findings, however, could produce new therapeutic strategies aimed at mobilizing the resident dental pulp stem cells to magnify the natural reparative capacity of teeth without the use of replacement materials.