再生领域的微小巨人:间充质干细胞衍生的细胞外囊泡作为下一代治疗手段
The tiny giants of regeneration: MSC-derived extracellular vesicles as next-generation therapeutics.
作者信息
Zhang Tianhe, Zhang Liang, Ma Xiaoxue, Song Wenliang
机构信息
Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, China.
Department of Neonatology, The Frist Hospital of China Medical University, Shenyang, China.
出版信息
Front Cell Dev Biol. 2025 Jul 17;13:1612589. doi: 10.3389/fcell.2025.1612589. eCollection 2025.
Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) are revolutionizing the field of regenerative medicine, becoming the core carriers of next-generation acellular therapeutic strategies. In contrast to traditional mesenchymal stem cell therapy, these nanoscale "regenerative tiny giants" offer significant advantages, including low immunogenicity, efficient biological barrier penetration, and stable storage. As natural bioactive molecular carriers, MSC-EVs precisely regulate the inflammatory response, angiogenesis, and tissue repair processes in target tissues by delivering functional RNA, proteins, and other signaling elements. They have demonstrated multidimensional therapeutic potential in diseases such as bone and joint regeneration, nerve function reconstruction, myocardial repair, and skin wound healing. Worldwide, 64 registered clinical trials have preliminarily validated the safety and applicability of MSC-EVs across various diseases. Notably, they have shown significant progress in treating severe coronavirus disease 2019 (COVID-19), ischemic stroke, and complex wound healing. However, the lack of standardization in production processes, insufficient targeting for delivery, and the scarcity of long-term biodistribution data remain core bottlenecks limiting the clinical translation of MSC-EVs. Future interdisciplinary technologies, including 3-dimensional (3D) dynamic culture, genetic engineering, and intelligent slow-release systems, are expected to facilitate the transition of MSC-EVs from the lab to large-scale applications. This shift may transform "injectable regenerative factors" into "programmable nanomedicines", offering new solutions for precision medicine.
间充质干细胞衍生的细胞外囊泡(MSC-EVs)正在革新再生医学领域,成为下一代无细胞治疗策略的核心载体。与传统的间充质干细胞疗法相比,这些纳米级的“再生小巨人”具有显著优势,包括低免疫原性、高效穿透生物屏障以及储存稳定。作为天然的生物活性分子载体,MSC-EVs通过递送功能性RNA、蛋白质和其他信号元件,精确调节靶组织中的炎症反应、血管生成和组织修复过程。它们在骨与关节再生、神经功能重建、心肌修复和皮肤伤口愈合等疾病中展现出多维治疗潜力。在全球范围内,64项注册临床试验已初步验证了MSC-EVs对各种疾病的安全性和适用性。值得注意的是,它们在治疗重症2019冠状病毒病(COVID-19)、缺血性中风和复杂伤口愈合方面已取得显著进展。然而,生产过程缺乏标准化、递送靶向性不足以及长期生物分布数据匮乏,仍然是限制MSC-EVs临床转化的核心瓶颈。未来的跨学科技术,包括三维(3D)动态培养、基因工程和智能缓释系统,有望推动MSC-EVs从实验室向大规模应用的转变。这种转变可能将“可注射的再生因子”转化为“可编程的纳米药物”,为精准医学提供新的解决方案。