Key Takeaways & Executive Findings
- •• Exosomes offer lower immunogenicity and no tumorigenic risk compared to stem cells, making them a safer alternative for oral tissue regeneration. • Exosomes demonstrate significant efficacy in regenerating dental pulp, periodontal tissues, craniofacial bone, salivary glands, nerves, and skin. • Engineering strategies such as preconditioning, isolation, and targeted modification can enhance exosome therapeutic potential. • Future research should focus on optimizing exosome production and clinical translation to overcome current limitations.
Abstract
BACKGROUND: Stem cells show a great potential in oral tissue regeneration but face challenges such as immune rejection and tumor formation. Exosomes are nanoscale extracellular vesicles secreted by cells, reducing immunogenicity and tumor risks while maintaining stem cell functions, such as promoting angiogenesis and tissue repair. OBJECTIVE: To summarize the mechanisms and roles of exosomes in oral tissue regeneration, explore exosome engineering strategies and the challenges and future directions in the application of exosomes in oral regenerative medicine. METHODS: The relevant literature published from the WanFang and PubMed databases from their inception to 2025 was searched using Chinese search terms “stem cells, exosomes, dental pulp regeneration, periodontal regeneration” and English search terms “exosomes, stem cells, dentistry, regenerate.” Finally, 94 articles were included for review and analysis. RESULTS AND CONCLUSION: (1) Exosomes have lower immunogenicity and no tumorigenic risk compared with stem cells. They are more stable and easier to store and transport. Additionally, exosomes can penetrate dense tissues for targeted delivery, avoiding ethical and immune rejection issues associated with stem cell therapy, making them a safer and more effective treatment option. (2) Exosomes have shown significant efficacy in regenerating dental pulp, periodontal tissues, craniofacial bone, salivary glands, nerves, and skin, promoting tissue repair and regeneration through multiple mechanisms, demonstrating broad application prospects. (3) Engineering strategies such as preconditioning, isolation and purification, and targeted modification can enhance exosome function, improving therapeutic potential and clinical feasibility. However, current technologies still have limitations, and further optimization is needed to promote widespread application of exosomes.
1. Introduction
Oral diseases directly affect oral physiological functions, causing pain, discomfort, and even endangering the overall health of patients [1]. Oral diseases are closely related to various systemic diseases, such as diabetes [2], cancer [3], and rheumatoid arthritis [4], necessitating new therapies capable of achieving oral tissue regeneration. Regenerative medicine is a promising approach to replenish defective tissues to restore normal physiological functions and reduce patient dependence on transplantation [5].
Dental-derived stem cells, including dental pulp stem cells, stem cells from human exfoliated deciduous teeth, and periodontal ligament stem cells, have shown multilineage differentiation potential, making them ideal for tissue engineering and therapy, capable of regenerating complex oral structures [6]. However, immune rejection, tumorigenicity, and ethical issues are unavoidable problems in stem cell therapy during tissue regeneration, highlighting the need for cell-free therapies.
Exosomes, first proposed by PAN et al. [7] in the 1980s, are extracellular vesicles secreted by parent cells and widely distributed in body fluids [8]. Exosomes exhibit biological functions similar to stem cells, such as promoting angiogenesis and tissue regeneration, while eliminating the risks of tumorigenesis and immune rejection associated with stem cells, making them an ideal choice for allogeneic therapy. Currently, exosomes have been widely applied in oral disease research and show great potential. This review summarizes the advantages of exosomes over stem cell therapy, systematically elaborates the applications and mechanisms of exosomes in oral tissue regeneration, and discusses the current challenges and future prospects of exosome therapy.
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Li Jiapeng, Zuleina·Abula, Jia Qianqian, Nigare·Yunusijiang, Sun Jiaqi, Zhao Jin, Wu Zeyu (2026). Advantages and potential of cell-derived exosomes in oral tissue regeneration. Chinese Journal of Tissue Engineering Research. https://doi.org/10.12307/2026.21356
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Frequently Asked Questions
What are exosomes and why are they advantageous for oral tissue regeneration?
Exosomes are nanoscale extracellular vesicles (30-150 nm) secreted by cells. They have lower immunogenicity, no tumorigenic risk, higher stability, and easier storage compared to stem cells. They can penetrate dense tissues and deliver signals, making them a safer and more effective option for oral tissue regeneration.
Which oral tissues can be regenerated using exosomes?
Exosomes have shown efficacy in regenerating dental pulp, periodontal tissues, craniofacial bone, salivary glands, nerves, and skin, promoting tissue repair through multiple mechanisms.
How can exosomes be engineered to enhance their therapeutic potential?
Engineering strategies such as preconditioning of parent cells, optimized isolation and purification methods, and targeted surface modification can enhance exosome functionality, improving their therapeutic potential and clinical feasibility.
What are the current challenges in exosome-based therapy for oral regeneration?
Challenges include large-scale production, standardization of isolation methods, targeted delivery efficiency, and understanding the molecular mechanisms of exosome-mediated regeneration. Further optimization is needed for clinical translation.
What is the future direction of exosome research in oral regenerative medicine?
Future research should focus on elucidating the molecular mechanisms of exosomal miRNAs in regulating signaling pathways, improving engineering strategies, and addressing clinical translation issues to maximize therapeutic efficiency.
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