A perfused human blood-brain barrier on-a-chip for high-throughput assessment of barrier function and antibody transport

Fluids and Barriers of the CNS
Nienke R WeversBirgit Obermeier

Abstract

Receptor-mediated transcytosis is one of the major routes for drug delivery of large molecules into the brain. The aim of this study was to develop a novel model of the human blood-brain barrier (BBB) in a high-throughput microfluidic device. This model can be used to assess passage of large biopharmaceuticals, such as therapeutic antibodies, across the BBB. The model comprises human cell lines of brain endothelial cells, astrocytes, and pericytes in a two-lane or three-lane microfluidic platform that harbors 96 or 40 chips, respectively, in a 384-well plate format. In each chip, a perfused vessel of brain endothelial cells was grown against an extracellular matrix gel, which was patterned by means of surface tension techniques. Astrocytes and pericytes were added on the other side of the gel to complete the BBB on-a-chip model. Barrier function of the model was studied using fluorescent barrier integrity assays. To test antibody transcytosis, the lumen of the model's endothelial vessel was perfused with an anti-transferrin receptor antibody or with a control antibody. The levels of antibody that penetrated to the basal compartment were quantified using a mesoscale discovery assay. The perfused BBB on-a-chip model shows presenc...Continue Reading

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Datasets Mentioned

BETA
AF110316
AY277254.1

Methods Mentioned

BETA
chips
flow cytometry
size exclusion chromatography
chip

Software Mentioned

FiJi
OrganoPlate
GraphPad Prism
ImageXpress
GraphPad

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