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©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
Extracellular vesicles from adipose-derived stem cells in bone regeneration: Mechanisms and therapeutic advances
An Lin, Jia-Lu Yu, Sheng-Meng Yuan, Ying-Feng Tang, Ke-Xin Yang, Yu-Hao Wang, Fang-Jun Huo, Zhao-Rui Jin, Qi Xiao, Chao Yang, Wei-Dong Tian
An Lin, Jia-Lu Yu, Sheng-Meng Yuan, Ke-Xin Yang, Yu-Hao Wang, Zhao-Rui Jin, Wei-Dong Tian, State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Engineering Research Center of Oral Translational Medicine, Ministry of Education & National Engineering Laboratory for Oral Regenerative Medicine & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
Ying-Feng Tang, Chao Yang, Department of Research and Development, Chengdu Shiliankangjian Biotechnology Co., Ltd, Chengdu 610213, Sichuan Province, China
Fang-Jun Huo, State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Engineering Research Center of Oral Translational Medicine, Ministry of Education & National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
Qi Xiao, School of Bioscience and Technology, Chengdu Medical College, Chengdu 610500, Sichuan Province, China
Co-corresponding authors: Chao Yang and Wei-Dong Tian.
Author contributions: Lin A was responsible for the conceptual design, literature collection, manuscript writing, and overall coordination of the review; Yu JL contributed to literature analysis, figure preparation, and manuscript revision; Yuan SM, Tang YF, Yang KX, and Wang YH assisted with data interpretation and critical literature review; Huo FJ and Jin ZR contributed to the refinement of the manuscript; Xiao Q helped with reference management and formatting; Yang C and Tian WD supervised the entire project, provided critical revisions, and are the corresponding authors responsible for the final approval of the manuscript. Yang C and Tian WD are co-corresponding authors, the two co-corresponding authors contributed equally to this review, and their collaboration ensured the scientific rigor and integrity of the work. All authors read and approved the final version of the manuscript.
Supported by the National Key Research and Development Program of China, No. 2022YFA1104400; and the National Natural Science Foundation of China, No. U21A20369.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Chao Yang, Department of Research and Development, Chengdu Shiliankangjian Biotechnology Co., Ltd, No. 366 Hemin Street, Chengdu High-Tech Zone, Chengdu 610213, Sichuan Province, China.
yangchao1207@qq.com
Received: June 3, 2025
Revised: July 17, 2025
Accepted: September 8, 2025
Published online: October 26, 2025
Processing time: 144 Days and 18.1 Hours
Extracellular vesicles (EVs) secreted by adipose-derived stem cells (ADSCs) have emerged as a promising cell-free therapeutic tool for bone regeneration. These EVs deliver a diverse array of bioactive molecules, including proteins, lipids, and nucleic acids, thereby modulating the bone microenvironment, activating key signaling pathways, and promoting bone regeneration. Innovative strategies involving preconditioning, genetic modification, and biomaterial-assisted delivery have been explored, with preclinical studies demonstrating synergistic effects that enhance targeting specificity and therapeutic efficacy. Functionally, EVs derived from ADSCs promote osteogenesis by enhancing osteoblast and mesenchymal stem cell activity, support angiogenesis through vascular endothelial growth factor signaling, and modulate inflammation by shifting macrophages from pro-inflammatory to anti-inflammatory phenotypes. In disease-specific contexts, they reduce cartilage degradation and support subchondral bone restoration in osteoarthritis, while in osteoporosis, they help restore the balance between bone formation and resorption and mitigate bone loss. Despite these promising developments, challenges remain in standardizing production protocols, optimizing delivery systems, and confirming long-term safety and efficacy in clinical settings. This review summarizes current insights into the mechanisms of EVs derived from ADSCs in bone-related diseases and highlights recent innovations and future directions that may accelerate their clinical application as a regenerative therapy.
Core Tip: Extracellular vesicles derived from adipose-derived stem cells exhibit significant potential in bone regeneration. They mediate osteogenesis, angiogenesis, and immunomodulation via bioactive molecules, with translational strategies including preconditioning, cargo engineering, and biomaterial integration. This review summarizes their efficacy in fractures, osteoarthritis, and osteoporosis, and discusses clinical translation challenges.
