Apoptotic vesicles activate autophagy in recipient cells to induce angiogenesis and dental pulp regeneration

作者：Zihan Li, Meiling Wu, Siying Liu, Xuemei Liu, Xuemei Liu, Yu Huan, Qingyuan Ye, Xiaoxue Yang, Guo Ht, Anqi Liu, Xiaoshan Yang, X J Yang, Feng Ding, Haokun Xu, J H Zhou, Shiyu Liu, S Y Liu, S Y Liu, Yan Jin, Kun Xuan · 发表于：Molecular Therapy · 年份：2022 · DOI：10.1016/j.ymthe.2022.05.006 · 被引用次数：123 · 研究领域：Extracellular vesicles in disease、Autophagy in Disease and Therapy、RNA Interference and Gene Delivery

Extracellular vesicles (EVs) derived from living cells play important roles in donor cell-induced recipient tissue regeneration. Although numerous studies have found that cells undergo apoptosis after implantation in an ischemic-hypoxic environment, the roles played by the EVs released by apoptotic cells are largely unknown. In this study, we obtained apoptotic vesicles (apoVs) derived from human deciduous pulp stem cells and explored their effects on the dental pulp regeneration process. Our work showed that apoVs were ingested by endothelial cells (ECs) and elevated the expression of angiogenesis-related genes, leading to pulp revascularization and tissue regeneration. Furthermore, we found that, at the molecular level, apoV-carried mitochondrial Tu translation elongation factor was transported and regulated the angiogenic activation of ECs via the transcription factor EB-autophagy pathway. In a beagle model of dental pulp regeneration in situ, apoVs recruited endogenous ECs and facilitated the formation of dental-pulp-like tissue rich in blood vessels. These findings revealed the significance of apoptosis in tissue regeneration and demonstrated the potential of using apoVs to promote angiogenesis in clinical applications.