The DOI matches its Crossref record; 74 of the 74 references it cites were found in a registry or an index.
A perfused human blood–brain barrier on-a-chip for high-throughput assessment of barrier function and antibody transport
Open accessAbstract
BACKGROUND: 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. METHODS: 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. RESULTS: cm/min, respectively). CONCLUSIONS: We demonstrate successful integration of a human BBB microfluidic model in a high-throughput plate-based format that can be used for drug screening purposes. This in vitro model shows sufficient barrier function to study the passage of large molecules and is sensitive to differences in antibody penetration, which could support discovery and engineering of BBB-shuttle technologies.
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Benchmarking in vitro tissue-engineered blood–brain barrier models
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Metadata
- Authors
- Wevers, N. R., Kasi, D. G., Gray, T., Wilschut, K. J., Smith, B., van Vught, R., Shimizu, F., Sano, Y., Kanda, T., Marsh, G., Trietsch, S. J., Vulto, P., Lanz, H. L., & Obermeier, B.
- Venue
- Fluids and Barriers of the CNS
- Published
- 2018-08-31
- Volume
- 15
- Issue
- 1
- Pages
- 23-23
- ISSN
- 2045-8118 (ISSN-L)
- OpenAlex
- W2887138305
- Cited by
- 353
- References
- 74
- FWCI
- 12.14
- Type
- journal article
- Language
- en
- Open access
- gold
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- Wevers, N. R., Kasi, D. G., Gray, T., Wilschut, K. J., Smith, B., van Vught, R., Shimizu, F., Sano, Y., Kanda, T., Marsh, G., Trietsch, S. J., Vulto, P., Lanz, H. L., & Obermeier, B. (2018). 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. https://doi.org/10.1186/s12987-018-0108-3
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
