Abstract:
: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.
journal_name
Cell Mol Bioengjournal_title
Cellular and molecular bioengineeringauthors
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 Wdoi
10.1007/s12195-016-0458-3subject
Has Abstractpub_date
2016-12-01 00:00:00pages
509-529issue
4eissn
1865-5025issn
1865-5033journal_volume
9pub_type
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journal_title:Cellular and molecular bioengineering
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journal_title:Cellular and molecular bioengineering
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journal_title:Cellular and molecular bioengineering
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