Song Yuqi, Liang Fengrui, Tian Weikun, Rayhill Erin, Ye Liping, Tian Xinghan
School of Clinical Medicine, Shandong Second Medical University, Weifang, Shandong, China.
Biology Department, Hamilton College, Clinton, NY, United States.
Front Pharmacol. 2025 Feb 10;16:1509418. doi: 10.3389/fphar.2025.1509418. eCollection 2025.
Mesenchymal stem cells (MSCs) and MSC-derived extracellular vesicles (MSC-EVs) are increasingly recognized for their therapeutic potential in regenerative medicine, driven by their capabilities in immunomodulation and tissue repair. However, MSCs present risks such as immunogenic responses, malignant transformation, and the potential to transmit infectious pathogens due to their intrinsic proliferative and differentiative abilities. In contrast, MSC-EVs, particularly exosomes (MSC-exosomes, 30-150 nm in diameter), offer a safer therapeutic profile. These acellular vesicles mitigate risks associated with immune rejection and tumorigenesis and are inherently incapable of forming ectopic tissues, thereby enhancing their clinical safety and applicability. This review highlights the therapeutic promise of MSC-exosomes especially focusing on the modulation of miRNA (one of bioactive molecules in MSC-EVs) profiles through various preconditioning strategies such as exposure to hypoxia, chemotherapeutic agents, inflammatory cytokines, and physical stimuli. Such conditioning is shown to optimize their therapeutic potential. Key miRNAs including miR-21, miR-146, miR-125a, miR-126, and miR-181a are particularly noted for their roles in facilitating tissue repair and modulating inflammatory responses. These functionalities position MSC-exosomes as a valuable tool in personalized medicine, particularly in the case of exosome-based interventions. Despite the potential of MSC-EVs, this review also acknowledged the limitations of traditional MSC therapies and advocates for a strategic pivot towards exosome-based modalities to enhance therapeutic outcomes. By discussing recent advances in detail and identifying remaining pitfalls, this review aims to guide future directions in improving the efficacy of MSC-exosome-based therapeutics. Additionally, miRNA variability in MSC-EVs presents challenges due to the diverse roles of miRNAs play in regulating gene expression and cell behavior. The miRNA content of MSC-EVs can be influenced by preconditioning strategies and differences in isolation and purification methods, which may alter the expression profiles of specific miRNAs, contributing to differences in their therapeutic effects.
间充质干细胞（MSCs）及其衍生的细胞外囊泡（MSC-EVs）因其免疫调节和组织修复能力，在再生医学中的治疗潜力日益受到认可。然而，由于其固有的增殖和分化能力，MSCs存在免疫原性反应、恶性转化以及传播感染性病原体的风险。相比之下，MSC-EVs，特别是外泌体（MSC-外泌体，直径30-150纳米），具有更安全的治疗特性。这些无细胞囊泡降低了与免疫排斥和肿瘤发生相关的风险，并且本质上无法形成异位组织，从而提高了它们的临床安全性和适用性。本综述强调了MSC-外泌体的治疗前景，特别关注通过各种预处理策略（如暴露于缺氧、化疗药物、炎性细胞因子和物理刺激）对miRNA（MSC-EVs中的生物活性分子之一）谱的调节。这种预处理被证明可以优化它们的治疗潜力。关键的miRNA，包括miR-21、miR-146、miR-125a、miR-126和miR-181a，因其在促进组织修复和调节炎症反应中的作用而特别受到关注。这些功能特性使MSC-外泌体成为个性化医学中的一种有价值的工具，特别是在基于外泌体的干预措施中。尽管MSC-EVs具有潜力，但本综述也承认传统MSC疗法的局限性，并主张战略性地转向基于外泌体的治疗方式以提高治疗效果。通过详细讨论最新进展并确定尚存的缺陷，本综述旨在为改善基于MSC-外泌体的治疗方法的疗效指引未来方向。此外，由于miRNA在调节基因表达和细胞行为中发挥的多种作用，MSC-EVs中的miRNA变异性带来了挑战。MSC-EVs的miRNA含量可能受到预处理策略以及分离和纯化方法差异的影响，这可能会改变特定miRNA的表达谱，导致其治疗效果的差异。
