biostudies-literatureChen CCAmerican Heart AssociationUC Irvine Academic Senate Council on Research, Computing, and LibrariesNCI NIH HHSNational Institutes of HealthNational Science Foundation509-529https://www.ebi.ac.uk/biostudies/studies/S-EPMC5382965biostudies-literatureUnknown9(4)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) <i>in vitro</i> under conditions that mimic the healthy and inflamed BBB <i>in vivo</i>. 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 <i>in vitro</i>. This study encourages further development of engineered exosomes as drug delivery vehicles or tracking tools for treating or monitoring neurological diseases.Cellular and molecular bioengineeringElucidation of Exosome Migration across the Blood-Brain Barrier Model In Vitro.PMC5382965NHLBI T3213BGIA17140099DP2 CA195763GRFPSIIG-2013-2014-251DP2CA195763-01Liu LWong CWGuo XEChacko JVDigman MAZhao WChen CCZhang SXFarhoodi HPPham VRiazifar MPone EJZimak JMa FSegaliny AfalseElucidation of Exosome Migration across the Blood-Brain Barrier Model In Vitro.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) <i>in vitro</i> under conditions that mimic the healthy and inflamed BBB <i>in vivo</i>. 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 <i>in vitro</i>. This study encourages further development of engineered exosomes as drug delivery vehicles or tracking tools for treating or monitoring neurological diseases.2016-01-01T00:00:00Z2016 Dec2024-11-21T07:48:45.729Z2019-03-27T02:40:37ZS-EPMC53829652839284010.1007/s12195-016-0458-3