Ragni Enrico
IRCCS Ospedale Galeazzi - Sant'Ambrogio, Laboratorio di Biotecnologie Applicate all'Ortopedia, 20157 Milano, Italy.
Front Biosci (Landmark Ed). 2025 May 30;30(6):36405. doi: 10.31083/FBL36405.
Extracellular vesicles (EVs) are nanoscale, membrane-enclosed structures that are secreted by nearly all cell types. EVs include small EVs (exosomes), large EVs (microvesicles), and apoptotic bodies, which are distinguished by their biogenesis and size. EV biogenesis involves endosomal pathways or direct budding from the plasma membrane, influenced by cellular states and external stimuli. The complex composition of EVs, proteins, lipids, RNA, DNA, and metabolites reflects their cell of origin, enabling EVs to mediate intercellular communication. EV uptake by recipient cells occurs via endocytosis, membrane fusion, or receptor-ligand interactions, influencing diverse physiological and pathological processes. Indeed, the biological roles of EVs range from immune modulation to tissue repair and contributions to cancer, neurodegeneration, musculoskeletal pathologies, and other disorders. Advances in isolation methods, including ultracentrifugation, size exclusion chromatography, and immunoaffinity techniques, have improved the purity and yield of EVs. Characterization technologies, such as nanoparticle tracking analysis, electron microscopy, and omics approaches, provide insights into their heterogeneity and functional cargo. Thus, EVs hold promise as non-invasive biomarkers for disease diagnosis and prognosis, offering high specificity and stability. Furthermore, the natural biocompatibility, ability to cross biological barriers, and capacity for functional cargo delivery of EVs position them as therapeutic tools and drug-delivery vehicles. Some of the most promising fields of application for EVs include cancer, neurodegeneration, and joint diseases; however, challenges remain in scaling production, achieving targeted delivery, and ensuring regulatory compliance. This review highlights recent advances in EV biology, isolation, and applications, emphasizing their crucial potential in precision medicine while identifying knowledge gaps and future research directions.
细胞外囊泡（EVs）是纳米级的、被膜包裹的结构，几乎所有细胞类型均可分泌。EVs包括小EVs（外泌体）、大EVs（微囊泡）和凋亡小体，它们可通过生物发生过程和大小来区分。EV的生物发生涉及内体途径或从质膜直接出芽，受细胞状态和外部刺激的影响。EVs复杂的组成成分，如蛋白质、脂质、RNA、DNA和代谢物，反映了它们的细胞来源，使EVs能够介导细胞间通讯。受体细胞对EV的摄取通过内吞作用、膜融合或受体-配体相互作用发生，影响多种生理和病理过程。事实上，EVs的生物学作用范围从免疫调节到组织修复，以及在癌症、神经退行性疾病、肌肉骨骼疾病和其他病症中的作用。包括超速离心、尺寸排阻色谱和免疫亲和技术在内的分离方法的进展，提高了EVs的纯度和产量。纳米颗粒跟踪分析、电子显微镜和组学方法等表征技术，为了解它们的异质性和功能货物提供了线索。因此，EVs有望作为疾病诊断和预后的非侵入性生物标志物，具有高特异性和稳定性。此外，EVs的天然生物相容性、穿越生物屏障的能力以及功能性货物递送能力，使其成为治疗工具和药物递送载体。EVs最有前景的一些应用领域包括癌症、神经退行性疾病和关节疾病；然而，在扩大生产规模、实现靶向递送和确保符合监管要求方面仍存在挑战。本综述重点介绍了EV生物学、分离和应用方面的最新进展，强调了它们在精准医学中的关键潜力，同时识别了知识空白和未来的研究方向。
