间充质干细胞外泌体临床用药合理性及安全性评价

doi:10.19803/j.1672-8629.20250133

摘要/Abstract

摘要： 目的系统评估间充质干细胞外泌体（MSC-Exo）的临床安全性及体内代谢特征,为该类新型生物治疗制剂的临床转化与合理应用提供参考。方法在临床试验注册平台（ClinicalTrials.gov）收集所有已注册的MSC-Exo相关临床研究项目,筛选其中涉及安全性评估的研究并进行归纳整理,并基于蛋白质量变化分析其稳定性与安全性之间的潜在关联。结果随着再生医学的快速发展,MSC-Exo作为无细胞治疗体系的重要组成部分,在多种疾病治疗中展现出广阔前景。本研究共纳入67项MSC-Exo临床研究,其中44项与安全性相关,涉及多个国家和多种疾病;同时,传代次数的增加导致MSC-Exo出现关键功能蛋白丢失、潜在风险蛋白富集及免疫调节功能不稳定等一系列变化,可能影响其治疗安全性及有效性。结论针对现有研究对MSC-Exo长期安全性及体内代谢机制数据不足,提出对临床受试者实施长期随访,建立并完善MSC-Exo的质量控制与评价体系的研究策略,同时强化上市后药物警戒,保障其临床用药安全。

关键词: 间充质干细胞, 外泌体, 安全性, 应用转化, 风险评估, 蛋白质组学

Abstract: Objective To assess the clinical safety and in vivo metabolic characteristics of mesenchymal stem cell-derived exosomes (MSC-Exo) in order to provide a reference for the clinical translation and sound applications of emerging biological therapeutic agents. Methods The Clinical Trials. gov registry was searched to identify all registered clinical trials related to MSC-Exo. Studies involving safety assessments were summarized and analyzed. The potential relationships between variations in protein quality and the stability and safety of MSC-Exo were investigated. Results With the rapid advancement of regenerative medicine, MSC-Exo, as a key component of cell-free therapy systems, promised wide applications in the treatment of a range of diseases. A total of 67 clinical trials around MSC-Exo were retrieved, 44 of which were focused on safety and involved a number of countries and diseases. As the number of passages increased, changes in the protein quality of MSC-Exo were observed, including loss of critical functional proteins, enrichment of potentially risky proteins, and instability in immunomodulatory functions, which might compromise its therapeutic safety and efficacy. Conclusion Given the limited data on the long-term safety and in vivo metabolic mechanisms of MSC-Exo in current research, it is recommended that long-term follow-up studies be conducted among clinical subjects and an integrated quality control and evaluation system be established for MSC-Exo. Furthermore, post-marketing pharmacovigilance should be strengthened to ensure clinical safety.

Key words: Mesenchymal Stem Cell, Exosomes, Safety, Applied Translation, Risk Assessment, Proteomics

中图分类号:

R979
R994.11

常铭洋, 周维, 孙源伯, 王睿, 沈磐, 倪喆鑫, 高月. 间充质干细胞外泌体临床用药合理性及安全性评价[J]. 中国药物警戒, 2025, 22(9): 967-974.

CHANG Mingyang, ZHOU Wei, SUN Yuanbo, WANG Rui, SHEN Pan, NI Zhexin, GAO Yue. Metabolism and Safety Evaluation of Mesenchymal Stem Cell-Derived Exosomes in vivo[J]. Chinese Journal of Pharmacovigilance, 2025, 22(9): 967-974.

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https://zgywjj.magtechjournal.com/CN/Y2025/V22/I9/967

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