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

• DOI: 10.1007/s12195-016-0458-3
• Publication Date: 2016-07-07T21:10:17Z
• 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 Ségaliny; Milad Riazifar; Victor Pham; Michelle A. Digman; Egest J. Pone; Weian Zhao
• Keywords: 1.1 Normal biological development and functioning; Biomedical Engineering; transcytosis; Humanized Gaussia luciferase; humanized Gaussia luciferase; Exocytosis; Article; 03 medical and health sciences; Underpinning research; endocytosis; exosome; Blood-brain barrier; Inflammation; 0303 health sciences; Neurosciences; blood-brain barrier; stroke; Endocytosis; Brain Disorders; 3. Good health; Stroke; Exosome; inflammation; 5.1 Pharmaceuticals; Drug delivery; Neurological; Development of treatments and therapeutic interventions; exocytosis; Transcytosis; Biotechnology

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.