2. Academic Validation
  3. Apoptotic vesicles activate autophagy in recipient cells to induce angiogenesis and dental pulp regeneration

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

  • Mol Ther. 2022 Oct 5;30(10):3193-3208. doi: 10.1016/j.ymthe.2022.05.006.
Zihan Li 1,  Meiling Wu 2,  Siying Liu 3,  Xuemei Liu 1,  Yu Huan 4,  Qingyuan Ye 5,  Xiaoxue Yang 2,  Hao Guo 2,  Anqi Liu 2,  Xiaoyao Huang 2,  Xiaoshan Yang 6,  Feng Ding 3,  Haokun Xu 3,  Jun Zhou 3,  Peisheng Liu 2,  Shiyu Liu 7,  Yan Jin 8,  Kun Xuan 9
Affiliations

Affiliations

  • 1 State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi Clinical Research Center for Oral Diseases, Department of Preventive Dentistry, School of Stomatology, The Fourth Military Medical University, 145West Changle Road, Xi'an, Shaanxi, China; State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, 145West Changle Road, Xi'an, Shaanxi, China.
  • 2 State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi Clinical Research Center for Oral Diseases, Department of Preventive Dentistry, School of Stomatology, The Fourth Military Medical University, 145West Changle Road, Xi'an, Shaanxi, China.
  • 3 State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, 145West Changle Road, Xi'an, Shaanxi, China.
  • 4 Department of Neurosurgery, Xijing Hospital, Air Force Medical University, Xi'an, Shaanxi, China.
  • 5 State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, 145West Changle Road, Xi'an, Shaanxi, China; State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Periodontology, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi, China.
  • 6 State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, 145West Changle Road, Xi'an, Shaanxi, China; Stomatology Hospital, Southern Medical University, Guangzhou, Guangdong, China.
  • 7 State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, 145West Changle Road, Xi'an, Shaanxi, China. Electronic address: liushiyu@vip.163.com.
  • 8 State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, 145West Changle Road, Xi'an, Shaanxi, China. Electronic address: yanjin@fmmu.edu.cn.
  • 9 State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi Clinical Research Center for Oral Diseases, Department of Preventive Dentistry, School of Stomatology, The Fourth Military Medical University, 145West Changle Road, Xi'an, Shaanxi, China. Electronic address: xuankun@fmmu.edu.cn.
PMID: 35538661 DOI: 10.1016/j.ymthe.2022.05.006
Abstract

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.

Keywords

MSC; angiogenesis; apoptotic vesicles; autophagy; dental pulp regeneration.

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