口腔疾病防治 (Oct 2024)
Research progress on dental mesenchymal stem cell-derived exosomes in periodontal immune regulation
Abstract
Exosomes (EXOs) are important mediators of intercellular communication that contain a variety of substances, including miRNA, mRNA, DNA, and protein molecules, which can act on target cells and have broad medical prospects as “cell-free therapy”. The inclusion of EXOs varies with the type and state of the donor cell, thus EXOs from different cell types may exhibit different biological effects. Dental mesenchymal stem cell (DMSC)-derived EXOs (DMSC-EXOs) have gained increasing research attention in the fields of tissue regenerative medicine and immune regulation. Current research on EXOs is focused on the homeostasis between proinflammatory (M1)/anti-inflammatory (M2) macrophages and T-helper 17 (Th17)/regulatory T (Treg) cells during periodontal immune regulation. Studies have shown that DMSC-EXOs can promote the transformation of macrophages and T cells and that this function may be dependent on the surrounding microenvironment and the tissue origin of stem cells. For instance, miR-1246 in dental pulp stem cell-derived EXOs promotes M2 macrophage polarization by inhibiting nuclear factor kappa-B (NF-κB) p65. Meanwhile, EXOs derived from stem cells from apical papilla promote DNA demethylase Tet2-mediated demethylation of FoxP3, maintain stable FoxP3 expression, and promote Treg cell transformation, thus alleviating local inflammation in periodontitis. In addition, the immunomodulatory activities of DMSC-EXOs can be affected by inflammatory factors. For example, EXOs derived from lipopolysaccharide-preconditioned dental follicle stem cells can reduce the receptor activator of NF-κB ligand/osteoprotegerin ratio through the reactive oxygen species (ROS)/c-Jun N-terminal kinase signaling pathway and promote M2 macrophage polarization through the ROS/extracellular signal-regulated kinase signaling pathway. Additionally, EXOs derived from gingiva-derived mesenchymal stem cells pretreated with tumor necrosis factor-α and interferon-α proinflammatory cytokines can promote M2 macrophage polarization through high expression of CD73 and CD5L, while EXOs derived from inflammatory periodontal ligament stem cells can promote M1 macrophage polarization. This article reviews the research progress on the immunoregulation and effects of DMSC-EXOs on the homeostasis of M1/M2 macrophages and Th17/Treg cells during periodontal immune regulation and provides a reference for the treatment of periodontitis using DMSC-EXOs.
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