Fu YJ, Jian J, Liu C, Yi YF, Ding YT, Wen J, Li YF, Guo QJ. Application of stem cell-derived exosomes in bone and joint diseases: Recent advances enabled by diverse carrier technologies. World J Stem Cells 2025; 17(11): 113631 [DOI: 10.4252/wjsc.v17.i11.113631]
Corresponding Author of This Article
Jie Wen, Associate Professor, Department of Pediatric Orthopedics, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, No. 61 Jiefang West Road, Changsha 410013, Hunan Province, China. cashwj@qq.com
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Orthopedics
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Minireviews
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This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
Nov 26, 2025 (publication date) through Nov 26, 2025
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World Journal of Stem Cells
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1948-0210
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Fu YJ, Jian J, Liu C, Yi YF, Ding YT, Wen J, Li YF, Guo QJ. Application of stem cell-derived exosomes in bone and joint diseases: Recent advances enabled by diverse carrier technologies. World J Stem Cells 2025; 17(11): 113631 [DOI: 10.4252/wjsc.v17.i11.113631]
World J Stem Cells. Nov 26, 2025; 17(11): 113631 Published online Nov 26, 2025. doi: 10.4252/wjsc.v17.i11.113631
Application of stem cell-derived exosomes in bone and joint diseases: Recent advances enabled by diverse carrier technologies
Ya-Jun Fu, Jie Jian, Can Liu, Yang-Fei Yi, Yi-Tong Ding, Jie Wen, Yu-Fei Li, Qing-Jun Guo
Ya-Jun Fu, Can Liu, Yang-Fei Yi, Yi-Tong Ding, Yu-Fei Li, Department of Anatomy, Hunan Normal University, Changsha 410013, Hunan Province, China
Jie Jian, Department of Clinical Medicine, Hebei Medical University, Shijiazhuang 050017, Hebei Province, China
Jie Wen, Department of Pediatric Orthopedics, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha 410013, Hunan Province, China
Qing-Jun Guo, Department of General Surgery and Operative Surgery, Hebei Medical University, Shijiazhuang 050017, Hebei Province, China
Co-first authors: Ya-Jun Fu and Jie Jian.
Co-corresponding authors: Jie Wen and Qing-Jun Guo.
Author contributions: Fu YJ and Jian J contribute equally to this study, they shared co-first authors. Fu YJ contributed to the conceptualization; Jian J contributed to the investigation; Liu C contributed to the formal analysis; Yi YF contributed to the methodology; Ding YT participated in the data curation; Wen J contributed to the validation; Li YF contributed to the supervision; Guo QJ contributed to the visualization. Wen J and Guo QJ revised the paper and they shared the co-corresponding author.
Supported by the Science Project of Hunan Provincial Healthy Commission, No. 20230844.
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: Jie Wen, Associate Professor, Department of Pediatric Orthopedics, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, No. 61 Jiefang West Road, Changsha 410013, Hunan Province, China. cashwj@qq.com
Received: August 31, 2025 Revised: September 25, 2025 Accepted: November 5, 2025 Published online: November 26, 2025 Processing time: 88 Days and 13.5 Hours
Abstract
Bone and joint diseases, such as osteoarthritis, exhibit significant pathological complexity. Current treatment modalities possess notable limitations, driving the development of cell-free regenerative treatment strategies centered on stem cell-derived exosomes, particularly mesenchymal stem cell-derived exosomes. Despite the promise of mesenchymal stem cell-derived exosomes, several challenges impede their clinical translation. These include rapid in vivo clearance of exosomes, insufficient targeting specificity, and the difficulty of dynamically regulating the pathological microenvironment with a single delivery approach. In recent years, optimizing exosome functionality and achieving precise delivery through carrier technologies has emerged as a pivotal strategy to overcome these barriers. This review systematically evaluates the latest advancements in cutting-edge carrier technologies. These encompass biomaterial scaffolds (e.g., three-dimensional bio-printed GA/HA composite scaffolds), hydrogels, engineered and modified exosomes (e.g., cartilage affinity peptide CAP-exoASO), and nanomicrosphere co-loading systems. Research findings demonstrate that these carrier technologies enhance cartilage repair and anti-inflammatory effects via multiple mechanisms, including extending the half-life of exosomes, improving cartilage-targeting specificity, and enabling synergistic immune regulation, such as promoting M2 macrophage polarization. Preclinical studies have validated the potential of these carrier technologies. However, critical issues remain, including standardizing production processes, ensuring long-term biological safety, and evaluating cross-species efficacy. Looking ahead, multimodal delivery systems integrating gene editing, intelligent responsive materials, and personalized treatment strategies are expected to revolutionize bone and joint disease treatment by transitioning from symptom alleviation to functional reconstruction.
Core Tip: Bone and joint diseases, such as osteoarthritis, exhibit significant pathological complexity. Current treatment modalities possess notable limitations, driving the development of cell-free regenerative treatment strategies centered on stem cell-derived exosomes, particularly mesenchymal stem cell-derived exosomes. Despite the promise of mesenchymal stem cell-derived exosomes, several challenges impede their clinical translation. In recent years, optimizing exosome functionality and achieving precise delivery through carrier technologies has emerged as a pivotal strategy to overcome these barriers. This review systematically evaluates the latest advancements in cutting-edge carrier technologies. Looking ahead, multimodal delivery systems integrating gene editing, intelligent responsive materials, and personalized treatment strategies are expected to revolutionize bone and joint disease treatment by transitioning from symptom alleviation to functional reconstruction.
