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Mesenchymal stem cell–derived extracellular vesicles in periodontal bone repair

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Abstract

Periodontitis is a chronic inflammatory disease that destroys tooth-supporting structures and poses significant public health challenges due to its high prevalence and links to systemic health conditions. Traditional treatments are effective in reducing the inflammatory response and improving the clinical symptoms of periodontitis. However, these methods are challenging to achieve an ideal treatment effect in alveolar bone repair. Mesenchymal stem cells (MSCs) represent a potential alternative for the treatment of periodontal bone defects due to their self-renewal and differentiation capabilities. Recent research indicates that MSCs exert their effects primarily through paracrine mechanisms. Mesenchymal stem cell–derived extracellular vesicles (MSC-EVs) serve as pivotal mediators in intercellular communication, transferring microRNAs (miRNAs), messenger RNAs (mRNAs), proteins, and cytokines to recipient cells, thereby emulating the therapeutic effects of MSCs. In periodontitis, MSC-EVs play a pivotal role in immunomodulation and bone remodeling, thereby facilitating periodontal bone repair. As a cell-free therapy, MSC-EVs demonstrate considerable clinical potential due to their specialized membrane structure, minimal immunogenicity, low toxicity, high biocompatibility, and nanoscale size. This review indicates that MSC-EVs represent a promising approach for periodontitis treatment, with the potential to overcome the limitations of traditional therapies and offer a more effective solution for bone repair in periodontal disease. In this review, we introduce MSC-EVs, emphasizing their mechanisms and clinical applications in periodontal bone repair. It synthesizes recent advances, existing challenges, and future prospects to present up-to-date information and novel techniques for periodontal regeneration and to guide the improvement of MSC-EV therapy in clinical practice.

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Funding

This work was supported by grants from the National Natural Science Foundation of China (32271365) and the Key Project of Sichuan Province (Grant No. 2023YFS0151).

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  1. Mengbing Chen and Bo Huang contributed equally to this work.

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  1. State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases &, Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, Sichuan, China

    Mengbing Chen, Bo Huang & Xiaoxia Su

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All authors contributed to the article conception and design. Methodology, investigation, and visualization were performed by Mengbing Chen, Bo Huang, and Xiaoxia Su. The first draft of the manuscript was written by Mengbing Chen and Bo Huang, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Chen, M., Huang, B. & Su, X. Mesenchymal stem cell–derived extracellular vesicles in periodontal bone repair. J Mol Med 103, 137–156 (2025). https://doi.org/10.1007/s00109-025-02513-4

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