Elucidation of Exosome Migration Across the Blood-Brain Barrier Model In Vitro

Overview

Journal Cell Mol Bioeng

Publisher Springer

Specialty Biomedical Engineering

Date 2017 Apr 11

PMID 28392840

Citations 255

Authors

Claire C Chen

Linan Liu

Fengxia Ma

Chi W Wong

Xuning E Guo

Jenu V Chacko

Henry P Farhoodi

Shirley X Zhang

Jan Zimak

Aude Segaliny

Milad Riazifar

Victor Pham

Michelle A Digman

Egest J Pone

Weian Zhao

Affiliations

Soon will be listed here.

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) under conditions that mimic the healthy and inflamed BBB . 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 . This study encourages further development of engineered exosomes as drug delivery vehicles or tracking tools for treating or monitoring neurological diseases.

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