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World J Stem Cells. Mar 26, 2026; 18(3): 114746
Published online Mar 26, 2026. doi: 10.4252/wjsc.v18.i3.114746
Published online Mar 26, 2026. doi: 10.4252/wjsc.v18.i3.114746
Human amniotic mesenchymal stem cell-derived small extracellular vesicles repair of jaw osteoradionecrosis
Hai-Fei Zhou, Fan Xu, Jian-Feng Li, Hua Yuan, Yi-Feng Bian, Yu-Li Wang, Yi-Fei Du, Department of Oral and Maxillofacial Surgery, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
Jia-Min Xu, Department of Stomatology, Chengdu Seventh People’s Hospital, Chengdu 610213, Sichuan Province, China
Jie Li, Department of Stomatology, Yangzhou Hospital of Traditional Chinses Medicine, Yangzhou 225000, Jiangsu Province, China
Yi Yu, Department of Anesthesiology, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
Co-first authors: Hai-Fei Zhou and Jia-Min Xu.
Co-corresponding authors: Yu-Li Wang and Yi-Fei Du.
Author contributions: Zhou HF and Xu JM contributed to acquiring and analyzing data from experiments, they contributed equally to this manuscript and are co-first authors; Yuan H, Wang YL, and Du YF contributed to conceptualization; Zhou HF, Xu JM, Li J, Xu F, Li JF, Yu Y, and Bian YF contributed to methodology; Xu JM, Xu F, and Li JF contributed to software; Du YF contributed to validation; Yuan H, Wang YL, and Du YF contributed to project administration and supervision; Du YF and Wang YL contributed to funding acquisition, writing the original draft and writing, review & editing with help from the other authors, they contributed equally to this manuscript and are co-corresponding authors.
Supported by Jiangsu Province Capability Improvement Project Through Science, Technology and Education-Jiangsu Provincial Research Hospital Cultivation Unit, No. YJXYYJSDW4; Jiangsu Provincial Medical Innovation Center, No. CXZX202227; the Project Funded by Jiangsu Provincial Commission of Health and Family Planning, No. BJ18035; and Nanjing Specific Program of Health and Technology Development, No. YKK23295.
Institutional review board statement: All experiments were approved by the ethics and research committee of Nanjing Medical University (Approval No. PJ2022-062-001).
Institutional animal care and use committee statement: All animal studies (including the rat euthanasia procedure) were performed in compliance with the regulations and guidelines of institutional animal care for Nanjing Medical University and conducted according to the Declaration of Helsinki and the IACUC guidelines (Approval No. IACUC-2310104).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: All data can be supplied for reasonable requests.
Corresponding author: Yi-Fei Du, MD, PhD, Associate Professor, Department of Oral and Maxillofacial Surgery, The Affiliated Stomatological Hospital of Nanjing Medical University, No. 1 Shanghai Road, Nanjing 210029, Jiangsu Province, China. dyf@njmu.edu.cn
Received: September 28, 2025
Revised: November 7, 2025
Accepted: January 22, 2026
Published online: March 26, 2026
Processing time: 179 Days and 7.2 Hours
Revised: November 7, 2025
Accepted: January 22, 2026
Published online: March 26, 2026
Processing time: 179 Days and 7.2 Hours
Core Tip
Core Tip: The small extracellular vesicles from human amniotic mesenchymal stem cells (hAMSCs-sEVs) enhanced tooth socket healing in rats with osteoradionecrosis of the jaw, increasing bone formation and expression of osteogenic (collagen-1, alkaline phosphatase) as well as angiogenic (CD31, vascular endothelial growth factor) markers. In vitro, hAMSCs-sEVs reversed the inhibition of osteogenesis and angiogenesis by reactivating the phosphatidylinositol 3-kinase/protein kinase B and Wnt/β-catenin signaling pathways, respectively, as confirmed by pathway inhibitors. These findings indicate that hAMSCs-sEVs facilitate osteoradionecrosis of the jaw bone healing by reversing radiation-impaired osteogenesis and angiogenesis via key signaling pathways.