Odontogenic exosomes simulating the developmental microenvironment promote complete regeneration of pulp-dentin complex in vivo

作者：Yifan Wang, Jing Mao, Yujie Wang, Rui Wang, Nan Jiang, Xiaohan Hu, Xin Shi · 发表于：Journal of Advanced Research · 年份：2025 · DOI：10.1016/j.jare.2024.12.048 · 被引用次数：19 · 研究领域：Extracellular vesicles in disease、Mesenchymal stem cell research、Bone and Dental Protein Studies

DPSC-Od-Exos from DPSCs undergoing initial odontogenic differentiation facilitated complete regeneration of pulp-dentin complex by enhancing odontogenesis, angiogenesis, and neurogenesis, shedding light on their promising prospects in advancing regenerative endodontic therapy. • Compared with normal exosomes derived from dental pulp stem cells (DPSC-Exos), exosomes secreted by DPSCs undergoing initial odontogenic differentiation (DPSC-Od-Exos) elicited a more robust enhancement on the proliferation and migration as well as odontogenic, endothelial, and neurogenic differentiation of DPSCs. • DPSC-Od-Exos were superior to DPSC-Exos in prompting the proliferative, migratory, and angiogenic potential of human umbilical vein endothelial cells (HUVECs). • As reveled by the Matrigel plug assay, DPSC-Od-Exos performed better than DPSC-Exos in ameliorating the formation of vascular tube-like structures of DPSCs and HUVECs. • After subcutaneous transplantation with DPSCs, DPSC-Od-Exos contributed to the regeneration of complete pulp-dentin complex in tooth root fragments, which encompassed enriched neurovascular structures and a continuous layer of odontoblast-like cells extending their cytoplasmic projections into the newly formed dentinal tubules. Establishing an optimized regenerative microenvironment for pulp-dentin complex engineering has become increasingly critical. Recently, exosomes have emerged as favorable biomimetic nanotherapeutic tools to simulate the developmental microe...