Abstract
Exosomes are vesicles involved in intercellular communication. Their membrane structure and core content is largely dependent on the cell of origin. Exosomes have been investigated both for their biological roles and their possible use as disease biomarkers and drug carriers. These potential technological applications require the rigorous characterization of exosomal blood brain barrier permeability and a description of their lipid bilayer composition. To achieve these goals, we have established a 3D static blood brain barrier system based on existing systems for liposomes and a complementary LC-MS/MS and 31P nuclear magnetic resonance methodology for the analysis of purified human plasma-derived exosome-like vesicles. Results show that the isolated vesicles pass the blood brain barrier and are taken up in endothelial cells. The compositional analysis revealed that the isolated vesicles are enriched in lyso phospholipids and do not contain phosphatidylserine. These findings deviate significantly from the composition of exosomes originating from cell culture, and may reflect active removal by macrophages that respond to exposed phosphahtidylserine.
Highlights
Delivery of therapeutic agents to the brain is challenging due to the blood-brain barrier (BBB), a highly selective membrane that separates circulating blood from the brain extracellular fluid in the central nervous system [1]
We analyzed the isolated extracellular vesicles (EVs) by SDS PAGE, Coomassie Brilliant Blue (CBB) staining, western blot (WB), Abs spectrometry and dynamic light scattering (DLS) to determine the purity, size and homogeneity (Fig 1 and S1 Fig)
We identified uptake of our plasma derived EVs in the hCMEC/D3 cells line (Figs 2 and 3), supporting the findings of Chen et al 2016 who identified internalization of exosomes derived from HEK 293T cells in endothelial cells [40]
Summary
Delivery of therapeutic agents to the brain is challenging due to the blood-brain barrier (BBB), a highly selective membrane that separates circulating blood from the brain extracellular fluid in the central nervous system [1]. The stringent selectivity of the barrier makes treatment of neurological diseases notoriously difficult. More than 98% of small-molecule drugs and almost 100% of large-molecule drugs, including peptides, recombinant proteins, monoclonal antibodies, genes and short interfering RNAs (siRNAs) cannot cross the BBB [2]. Exosomes have emerged as promising vehicles for the transport of therapeutics across the BBB, giving promise for treatment of Alzheimer disease, Parkinson disease, epilepsy, mental disorders and more [3,4]. Several mechanisms allow compounds to cross the BBB and prevent harmful compounds from entering the brain, and their normal function is critical for proper neuronal.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
