Wang Xu, Guo Dan, He Chengmei, Wang Xiaoxi, Wei Yi, Zhang Fengchun, Wang Li, Yang Yanlei
Clinical Biobank, Department Medical Research Central, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Rheumatology and Clinical Immunology, Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, National Clinical Research Center for Dermatologic and Immunologic Diseases, Beijing, China.
Stem Cell Res Ther. 2025 May 28;16(1):265. doi: 10.1186/s13287-025-04360-z.
Aging leads to a gradual decline in immune function, termed immunosenescence, which significantly elevates the susceptibility to infections, cancers, and other aging-related diseases. Recent advancements have shed light on the molecular underpinnings of immune aging and pioneered novel therapeutic interventions to counteract its effects. Mesenchymal stem cells (MSCs)-a type of multipotent stromal cells with regenerative potential, low immunogenicity, and strong immunomodulatory properties-are increasingly recognized as a promising therapeutic option to reverse or alleviate immunosenescence-related dysfunction. This review systematically summarizes recent discoveries on how MSCs counteract immune aging, particularly their ability to rejuvenate aged immune cells and restore immune homeostasis. It also addresses key challenges, such as variations in MSC sources, donor variability, and the lack of standardized protocols, while proposing future directions to enhance therapeutic precision. Although preclinical and clinical studies highlight the potential of MSC-based strategies for delaying immunosenescence, critical issues remain unresolved, including long-term safety and efficacy, optimizing cell delivery systems, and elucidating context-specific mechanisms. Addressing these challenges will accelerate the development of MSC-based therapies to combat aging-associated immune decline.
衰老会导致免疫功能逐渐下降，即免疫衰老，这会显著增加感染、癌症和其他与衰老相关疾病的易感性。最近的进展揭示了免疫衰老的分子基础，并开创了对抗其影响的新型治疗干预措施。间充质干细胞（MSCs）——一种具有再生潜力、低免疫原性和强大免疫调节特性的多能基质细胞——越来越被认为是一种有前景的治疗选择，可用于逆转或减轻与免疫衰老相关的功能障碍。本综述系统地总结了关于MSCs如何对抗免疫衰老的最新发现，特别是它们使衰老免疫细胞恢复活力和恢复免疫稳态的能力。它还讨论了关键挑战，如MSCs来源的差异、供体变异性以及缺乏标准化方案，同时提出了提高治疗精准度的未来方向。尽管临床前和临床研究突出了基于MSCs的策略延缓免疫衰老的潜力，但关键问题仍未解决，包括长期安全性和有效性、优化细胞递送系统以及阐明特定背景下的机制。应对这些挑战将加速基于MSCs的疗法的开发，以对抗与衰老相关的免疫衰退。
