SHED aggregate derived exosomes-shuttled miR-222 promotes the angiogenic properties of periodontal ligament stem cells and enhances periodontal regeneration

作者：Feng Zhou, Jia Guo, Zhiwei Dong, Wanmin Zhao, Xiaoning He, Meiling Wu, Shuyi Li, Bei Li, Miao Zhou · 发表于：Translational dental research. · 年份：2025 · DOI：10.1016/j.tdr.2025.100032 · 被引用次数：3 · 研究领域：Periodontal Regeneration and Treatments、Mesenchymal stem cell research、Extracellular vesicles in disease

Periodontal ligament stem cells (PDLSCs) aggregate is still limited in clinical application due to a lack of angiogenesis. This study aimed to investigate the effects and underlying mechanism of exosomes derived from stem cells from human exfoliated deciduous teeth (SHED) aggregate (SA-Exo) on the aggregate formation and angiogenic properties of PDLSCs. SA-Exo was isolated by ultracentrifugation. The effect of SA-Exo on the aggregate formation and angiogenic differentiation of PDLSCs was evaluated by investigating extracellular matrix (ECM) deposition and tube formation assay. microRNA (miRNA) sequencing was employed to screen for different miRNA expression. The effect of targeting miRNA on ECM deposition and angiogenesis of PDLSCs aggregate was investigated after overexpression and inhibition of miRNA. Alveolar bone defect rat models were established to evaluate the effect of the PDLSCs aggregate and SA-Exo combination on alveolar bone regeneration. SA-Exo could significantly enhance the ECM deposition and angiogenic ability of PDLSCs. The expression of ECM-associated proteins (collagen type I and fibronectin), angiogenesis-related proteins (platelet derived growth factor, angiogenin, transforming growth factor-β receptor II), and related pathway (p-SMAD1/5 and p-SMAD2/3) were upregulated in PDLSCs aggregate with SA-Exo. Mechanistically, miR-222 was found relatively abundant in SA-Exo, which promoted ECM deposition and angiogenesis of PDLSCs. In vivo experiment further valid...