Doctoral Program in Medical Sciences, Faculty of Medicine, Pontificia Universidad Catolica de Chile, Santiago de Chile, Chile.
Advanced Center for Chronic Diseases, Santiago, Chile.
Fluids Barriers CNS. 2022 Jul 25;19(1):60. doi: 10.1186/s12987-022-00359-3.
Extracellular vesicles (EVs) are particles naturally released from cells that are delimited by a lipid bilayer and are unable to replicate. How the EVs cross the Blood-Brain barrier (BBB) in a bidirectional manner between the bloodstream and brain parenchyma remains poorly understood. Most in vitro models that have evaluated this event have relied on monolayer transwell or microfluidic organ-on-a-chip techniques that do not account for the combined effect of all cellular layers that constitute the BBB at different sites of the Central Nervous System. There has not been direct transcytosis visualization through the BBB in mammals in vivo, and evidence comes from in vivo experiments in zebrafish. Literature is scarce on this topic, and techniques describing the mechanisms of EVs motion through the BBB are inconsistent. This review will focus on in vitro and in vivo methodologies used to evaluate EVs transcytosis, how EVs overcome this fundamental structure, and discuss potential methodological approaches for future analyses to clarify these issues. Understanding how EVs cross the BBB will be essential for their future use as vehicles in pharmacology and therapeutics.
细胞外囊泡（EVs）是由脂质双层限定且不能复制的细胞自然释放的颗粒。EVs 如何在血流和脑组织之间以双向方式穿越血脑屏障（BBB），目前仍知之甚少。大多数评估这一事件的体外模型都依赖于单层 Transwell 或微流控器官芯片技术，这些技术无法解释构成中枢神经系统不同部位 BBB 的所有细胞层的综合效应。在哺乳动物体内还没有直接通过 BBB 的胞吞作用可视化的证据，而这一证据来自于斑马鱼的体内实验。关于这个主题的文献很少，描述 EVs 通过 BBB 运动机制的技术也不一致。这篇综述将重点介绍用于评估 EVs 胞吞作用的体外和体内方法，以及 EVs 如何克服这一基本结构，并讨论未来分析这些问题的潜在方法。了解 EVs 如何穿越 BBB 将对它们在药理学和治疗学中作为载体的未来应用至关重要。
