Antler stem cell-derived exosomes restore periodontal homeostasis in a rat model with diabetic periodontitis through enhancing ROS scavenging and osteogenesis

作者：Qianqian Guo, Sicong Ren, Antonio Libonati, Jiping Li, Zhen Wang, Jing Ren, Guokun Zhang, Linlin Gao, Hengxing Ba, Yuqin Shen, Chunyi Li · 发表于：Cell Death Discovery · 年份：2025 · DOI：10.1038/s41420-025-02800-6 · 被引用次数：6 · 研究领域：Oral microbiology and periodontitis research、Extracellular vesicles in disease、Periodontal Regeneration and Treatments

Diabetes mellitus (DM) exacerbates periodontitis as the high-glucose (HG) environment aggravates local inflammation and periodontal bone resorption. Restoring periodontal homeostasis and promoting periodontal bone repair/regeneration are major challenges for the treatment of diabetic periodontitis. This study introduces antler stem cell-derived exosomes (AnSC-exos) as a potent therapeutic for treating diabetic periodontitis via leveraging the shared cranial neural crest cell (CNCC) origin of antlers and periodontal tissues. Using a rat model of diabetic periodontitis, we demonstrate that AnSC-exos effectively alleviate tissue abnormalities and alveolar bone destruction and resorption in periodontitis under DM conditions; the outcome was significantly more potent than human bone marrow mesenchymal stem cell exosomes (hBMSC-exos). Mechanistically, AnSC-exos exhibited dual regenerative actions: (1) restoring the osteogenic ability of resident MSCs by not only reversing high glucose (HG)-induced suppression of proliferation and migration, but more importantly, enhancing cell survival, reducing cell death, and strengthening differentiation toward osteogenic lineages under HG conditions; and (2) attenuating inflammation through potently scavenging excessive ROS production induced by HG, and inhibiting HG-mediated p65 nuclear translocation, thereby leading to a reduced M1/M2 macrophage ratio. In conclusion, the superior efficacy of AnSC-exos highlights their tissue-specific regenera...