Elucidation of Exosome Migration across the Blood-Brain Barrier Model In Vitro.
Elucidation of Exosome Migration across the Blood-Brain Barrier Model In Vitro.
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DOI：
10.1007/s12195-016-0458-3
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发表时间：
2016-12
影响因子：
2.8
通讯作者：
Zhao W
中科院分区：
文献类型：
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作者：
Chen CC;Liu L;Ma F;Wong CW;Guo XE;Chacko JV;Farhoodi HP;Zhang SX;Zimak J;Ségaliny A;Riazifar M;Pham V;Digman MA;Pone EJ;Zhao W
将治疗剂递送至中枢神经系统（CNS）仍然是一个主要挑战，部分原因是血脑屏障（BBB）的存在。最近，细胞衍生的囊泡，特别是外泌体，已经成为一种有吸引力的载体，用于将药物靶向大脑，但它们是否或如何穿过BBB仍不清楚。在这里，我们研究了外泌体和脑微血管内皮细胞（BMEC）之间的相互作用，在体外的条件下，模拟健康和发炎的血脑屏障在体内。Transwell试验显示，携带有β-内酰胺酶的外泌体可以在中风样炎症条件下（TNF-α激活）穿过BMEC单层，但在正常条件下不能。共聚焦显微镜显示，外泌体通过内吞作用被BMEC内化，与内体共定位，实际上主要利用跨细胞途径交叉。总之，这些结果表明，细胞来源的外泌体可以在体外中风样条件下穿过BBB模型。这项研究鼓励进一步开发工程外泌体作为药物递送载体或跟踪工具，用于治疗或监测神经系统疾病。
The delivery of therapeutics to the central nervous system (CNS) remains a major challenge in part due to the presence of the blood-brain barrier (BBB). Recently, cell-derived vesicles, particularly exosomes, have emerged as an attractive vehicle for targeting drugs to the brain, but whether or how they cross the BBB remains unclear. Here, we investigated the interactions between exosomes and brain microvascular endothelial cells (BMECs) in vitro under conditions that mimic the healthy and inflamed BBB in vivo. Transwell assays revealed that luciferase-carrying exosomes can cross a BMEC monolayer under stroke-like, inflamed conditions (TNF-α activated) but not under normal conditions. Confocal microscopy showed that exosomes are internalized by BMECs through endocytosis, co-localize with endosomes, in effect primarily utilizing the transcellular route of crossing. Together, these results indicate that cell-derived exosomes can cross the BBB model under stroke-like conditions in vitro. This study encourages further development of engineered exosomes as drug delivery vehicles or tracking tools for treating or monitoring neurological diseases.