Human Umbilical Cord Mesenchymal Stem Cells and their Extracellular Vesicles Modulate Pro- and Anti-inflammatory Cytokines in Ligature-induced Periodontitis

Iran J Immunol. 2023 Dec 31;20(4):446-455. doi: 10.22034/iji.2023.100211.2683. Epub 2023 Dec 16.

Abstract

Background: Periodontitis is a chronic inflammatory condition that affects the tissues supporting the teeth, ultimately leading to tooth loss. Mesenchymal stem cells (MSCs) and their extracellular vesicles (EVs) play a crucial role in periodontitis by modulating the activities of gum cells and the immune system.

Objective: To investigate the therapeutic potential of human umbilical cord mesenchymal stem cells (hUCSCs) and EVs in regulating the inflammatory response associated with periodontitis.

Methods: hUCSCs were isolated, subjected to flow cytometry analysis of surface markers, and differentiated into adipocyte and osteocyte. hUCSC-EVs were isolated and characterized using flow cytometry and electron microscopy. A periodontitis animal model was established in 30 female C57Bl/6 mice. Experimental groups received hUCSCs or hUCSCs-EVs, or vehicles intravenously. Animals were monitored for 4 weeks, and the periodontal tissues were used to assess the effects of hUCSCs and hUCSCs-EVs on the expression of pro- (TNF-α, IFN-γ, and IL-17a) and anti-inflammatory cytokines (TGF-β, IL-10, and IL-4). The secretion of these cytokines by splenocytes was also evaluated using ELISA.

Results: The levels of IL-17a, IFN-γ, and TNFα significantly reduced, while TGF-β and IL-10 significantly increased in the periodontal tissues of the hUCSC and hUCSCEVs-treated mice. The expression of TNF-α, IFN-γ, and IL-17a significantly decreased, while the production of IL-10 and TGF-β significantly increased in splenocytes from the hUCSC and EVs-treated mice.

Conclusion: hUCSCs and their EVs have the potential to attenuate the inflammatory response associated with periodontitis, possibly by downregulating pro-inflammatory cytokines and upregulating anti-inflammatory ones.

Keywords: Anti-Inflammatory Cytokine; Extracellular Vesicles; Mesenchymal Stem Cells; Periodontitis; Pro-Inflammatory Cytokine.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents
  • Cytokines / metabolism
  • Extracellular Vesicles* / metabolism
  • Female
  • Humans
  • Interleukin-10 / metabolism
  • Interleukin-17 / metabolism
  • Mesenchymal Stem Cells*
  • Mice
  • Periodontitis* / metabolism
  • Periodontitis* / therapy
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha / metabolism
  • Umbilical Cord / metabolism

Substances

  • Cytokines
  • Interleukin-10
  • Interleukin-17
  • Tumor Necrosis Factor-alpha
  • Transforming Growth Factor beta
  • Anti-Inflammatory Agents