《生命科学》 2026, 38(4): 625-634
牙龈间充质干细胞以及外泌体在自身免疫性疾病中的应用和挑战
摘 要：
自身免疫性疾病（autoimmune diseases，ADs）发病率逐年上升，传统疗法存在显著局限。牙龈间充质干细胞（gingiva-derived mesenchymal stem cells，GMSCs）因其易获取、高增殖和强效免疫调节特性，在ADs治疗中展现出独特优势。本文系统综述了GMSCs及其来源的外泌体在ADs治疗中的应用基础和转化前景。核心内容包括GMSCs对固有免疫和适应性免疫系统的多靶点调控机制，以及相较于传统MSCs的潜在优势。GMSCs来源的外泌体（GMSCs-Exo）作为无细胞治疗载体，继承并拓展了GMSCs的治疗效应，为克服细胞疗法局限提供了新策略。然而，该领域临床转化仍面临关键挑战，如细胞/外泌体异质性、规模化生产、靶向递送效率和长期安全性评估等。本文深入总结了这些瓶颈，并展望了跨学科策略（如智能递送、类器官模型、人工智能、标准化体系）对未来发展的推动作用。本综述旨在为深入理解GMSCs及其外泌体在ADs治疗中的价值，推动下一代免疫疗法的研发提供参考。
通讯作者：郑颂国 , Email:Song.Zheng@shsmu.edu.cn
Abstract:
Autoimmune diseases (ADs) represent a growing global health burden, characterized by aberrant immune responses that attack self-tissues, leading to chronic inflammation and multi-organ damage. Conventional therapies, including corticosteroids, immunosuppressants, and biologics, often exhibit limited efficacy and substantial adverse effects, highlighting the urgent need for innovative therapeutic strategies. Gingival mesenchymal stem cells (GMSCs) have emerged as a promising candidate due to their ease of harvest, high proliferative capacity, and potent immunomodulatory properties. This review systematically examines the therapeutic potential of GMSCs and their secreted exosomes (GMSCs-Exo) in the context of ADs, with a focus on mechanistic insights, preclinical applications, and translational challenges. GMSCs exert multi-targeted immunoregulatory effects by modulating both innate and adaptive immunity. They induce macrophage polarization toward anti-inflammatory M2 phenotypes, inhibit pro-inflammatory dendritic cell and neutrophil activity, and reestablish T and B cell homeostasis by promoting regulatory T cell (Treg) expansion and suppressing pathogenic Th1/Th17 responses. Compared to conventional MSCs, GMSCs demonstrate superior immune suppression, enhanced proliferative capacity, minimal ethical concerns, and safer clinical profiles, making them particularly attractive for translational applications. GMSCs-Exo act as cell-free therapeutic vectors, delivering miRNAs, proteins, and other bioactive molecules to replicate and even extend the immunoregulatory effects of parental cells while circumventing risks associated with live cell transplantation. Preclinical studies indicate that GMSCs and GMSCs-Exo significantly ameliorate diverse autoimmune pathologies, including systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, type 1 diabetes, psoriasis, and allergic asthma, by targeting disease-specific inflammatory pathways, restoring immune tolerance, and promoting tissue repair. Nevertheless, clinical translation faces significant obstacles, such as donor heterogeneity, scalable production of exosomes, targeted delivery efficiency, and comprehensive long-term safety evaluation. Emerging interdisciplinary strategies, including engineered exosomes with surface modifications, intelligent delivery systems, organoid-based disease models, high-throughput omics analyses, and AI-guided predictive platforms, offer potential solutions to these challenges, advancing the field toward precision immunotherapy. In conclusion, GMSCs and their exosomes provide a transformative paradigm for ADs treatment, bridging immune modulation and regenerative therapy. Continued integration of bioengineering, computational biology, and translational medicine is essential to overcome current bottlenecks, optimize therapeutic efficacy, and establish standardized, safe, and scalable protocols for future clinical application. These advances may ultimately enable next-generation therapies that move from broad-spectrum immune suppression to precise, personalized intervention, achieving both disease remission and tissue regeneration.
Communication Author：ZHENG Song-Guo , Email:Song.Zheng@shsmu.edu.cn
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