Attempting to Make Periodontal Stem Cells More Active in the Inflammatory Conditions of Periodontitis

The state of chronic, unresolved inflammation in the diseased gums of periodontitis drives loss of bone and tissue. This occurs in part due to suppression of the activity of stem cells and other necessary participants in tissue maintenance processes. Researchers here evaluate an approach to forcing stem cells into greater activity under inflammatory conditions, by introducing naturally occurring lipids that are known to act in the mechanisms responsible for resolving inflammation. The work is carried out in cell cultures only, but is nonetheless interesting.

Periodontitis is a chronic inflammatory disease that affects supporting periodontal tissues surrounding the teeth, i.e., cementum, alveolar bone, and periodontal ligament, leading to extensive tooth loss in severe cases and impacting the systemic well-being of the patient. The understanding of chronic inflammatory disorders, including periodontitis, has been limited to the activation of pro-inflammatory mediators through a canonical pathway that is responsible for the exaggerated synthesis of cytokines such as IL-1β and TNF-α. However, it is now appreciated that the physiology of the inflammatory processes also involves a cascade of programmed and receptor-mediated events that determine the synthesis of endogenous specialized pro-resolving lipid mediators (SPMs), and the resolution of inflammation.

Specialized pro-resolving lipid mediators derived from ω-3 polyunsaturated fatty acids, including resolvins and maresins, have a wide array of functions, induce changes in local biofilm composition, reorganize host response, and enhance bacterial phagocytosis and efferocytosis of inflammatory cells during the immunological responses to microbial and inflammatory stimuli. Resolvin E1 (RvE1), which is derived from eicosapentaenoic acid, has been shown to promote periodontal regeneration inducing the formation of new alveolar bone, cementum, and improved fibrogenesis in an experimental model of periodontitis. Maresin MaR1, which is derived from docosahexaenoic acid, has been shown to have potent activity accelerating surgical wound healing in planaria, providing evidence for organ regeneration and tissue healing. Both RvE1 and MaR1 have the potential to stimulate pro-regenerative activities, regulate wound healing, and reverse tissue destruction.

Thus, we measured the impact of MaR1 and RvE1 in an in vitro model of human periodontal ligament stem cells (hPDLSCs) under stimulation with IL-1β and TNF-α. The data showed that the pro-inflammatory milieu suppresses pluripotency, viability, and migration of hPDLSCs; MaR1 and RvE1 both restored regenerative capacity by increasing hPDLSC viability, accelerating wound healing/migration, and up-regulating periodontal ligament markers and cementogenic-osteogenic differentiation. Together, these results demonstrate that MaR1 and RvE1 restore or improve the regenerative properties of highly specialized stem cells when inflammation is present and offer opportunities for direct pharmacologic treatment of lost tissue integrity.

Link: https://doi.org/10.3389/fimmu.2020.585530

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