Yang Y, Zhang GD, Yi L, Yang X, Han ZG, Song CY, Lu JS, Wang KY. Breaking the cycle of radiation-induced bone death: Human amniotic mesenchymal stem cell-derived small extracellular vesicles restore coupled osteo-angiogenic regeneration. World J Stem Cells 2026; 18(8): 119963 [DOI: 10.4252/wjsc.119963]
Corresponding Author of This Article
Kai-Yang Wang, Department of Orthopedic Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No. 600 Yishan Road, Shanghai 200233, China. ortho_wang@163.com
Research Domain of This Article
Orthopedics
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review-article
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Yang Y, Zhang GD, Yi L, Yang X, Han ZG, Song CY, Lu JS, Wang KY. Breaking the cycle of radiation-induced bone death: Human amniotic mesenchymal stem cell-derived small extracellular vesicles restore coupled osteo-angiogenic regeneration. World J Stem Cells 2026; 18(8): 119963 [DOI: 10.4252/wjsc.119963]
World J Stem Cells. Aug 26, 2026; 18(8): 119963 Published online Aug 26, 2026. doi: 10.4252/wjsc.119963
Breaking the cycle of radiation-induced bone death: Human amniotic mesenchymal stem cell-derived small extracellular vesicles restore coupled osteo-angiogenic regeneration
Yang Yang, Guo-Dong Zhang, Ling Yi, Xu Yang, Zeng-Gao Han, Chen-Yu Song, Jing-Shun Lu, Kai-Yang Wang
Yang Yang, Guo-Dong Zhang, Ling Yi, Zeng-Gao Han, Southern Central Hospital of Yunnan Province, The First People’s Hospital of Honghe State, Honghe Hani and Yi Autonomous Prefecture 661000, Yunnan Province, China
Xu Yang, Department of Radiology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing 210008, Jiangsu Province, China
Chen-Yu Song, Kai-Yang Wang, Department of Orthopedic Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China
Jing-Shun Lu, Department of Orthopedics, The First Affiliated Hospital of Wannan Medical College, Yijishan Hospital, Wuhu 241000, Anhui Province, China
Author contributions: Yang Y wrote and edited the manuscript; Zhang GD, Yi L, and Yang X contributed to review and edit; Han ZG and Song CY reviewed this paper; Lu JS and Wang KY conceived, reviewed, and revised this paper.
AI contribution statement: The authors declare that no AI tools were used in the preparation of this manuscript and the response to reviewers. As this is a review article, all work, including the critical evaluation of literature, is the original work of the authors.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Kai-Yang Wang, Department of Orthopedic Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No. 600 Yishan Road, Shanghai 200233, China. ortho_wang@163.com
Received: February 11, 2026 Revised: April 17, 2026 Accepted: May 25, 2026 Published online: August 26, 2026 Processing time: 190 Days and 16.8 Hours
Abstract
Osteoradionecrosis (ORN) is a severe, treatment-resistant complication of radiotherapy driven by disrupted osteo-angiogenic coupling, mitochondrial dysfunction, epigenetic silencing, and a chronic inflammatory-fibrotic microenvironment. This review highlights recent findings to suggest that small extracellular vesicles derived from human amniotic mesenchymal stem cells (hAMSC-sEVs) may represent a novel and effective cell-free therapeutic strategy for the treatment of ORN. The hAMSC-sEVs can act as a dynamic biological system to restore bone regeneration through four synergistic mechanisms: Rescuing bioenergetics via mitochondrial transfer, reactivating osteogenic programs through epigenetic remodeling, co-activating pro-regenerative signaling pathways, and reprogramming the immune niche by suppressing the senescence-associated secretory phenotype and promoting anti-inflammatory macrophage polarization. With ongoing advances in scalable production and targeted delivery, hAMSC-sEVs hold significant promise for clinical translation as a regenerative therapy for ORN.
Core Tip: Human amniotic mesenchymal stem cell-derived small extracellular vesicles represent a novel cell-free therapy for osteoradionecrosis. They reverse osteoradionecrosis progression through multi-target mechanisms - mitochondrial transfer, epigenetic reprogramming, pro-regenerative signaling activation, and immune microenvironment remodeling - offering a promising translational strategy for refractory radiotherapy-induced bone damage.
