Evidence map›Paper›PMID 30165870›Full record

ArticleFluids and barriers of the CNS2018

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

Nienke R Wevers, Dhanesh G Kasi, Taylor Gray, Karlijn J Wilschut, Benjamin Smith, Remko van Vught, Fumitaka Shimizu, Yasuteru Sano, Takashi Kanda, Graham Marsh and 4 more

Open access · goldAbstract read
In one paragraph

Article in Fluids and barriers of the CNS, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 191 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
191citing papers in PubMed, 4 pooled it
14.7field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

191 citing papers in PubMed, 4 syntheses or guidelines pooled it, 338 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Advances in Engineering Human Tissue Models.Frontiers in bioengineering and biotechnology · 2020
    Pooled it
  5. Review
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  9. Article
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  11. Article
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  13. Article
  14. Preclinical Models of Traumatic Brain Injury: Advances in In Vitro Models.Current neurology and neuroscience reports · 2026
    Review
  15. Review
  16. Article
  17. Observational
  18. Review
  19. HumanBioactive materials · 2026
    Article
  20. Review

131 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 3 institutions in 3 countries.

Nienke R WeversMimetas BV, J.H. Oortweg 19, 2333 CH, Leiden, The Netherlands. n.wevers@mimetas.com.
Dhanesh G KasiMimetas BV, J.H. Oortweg 19, 2333 CH, Leiden, The Netherlands.
Taylor GrayBiogen, 225 Binney Street, Cambridge, MA, 02142, USA.
Karlijn J WilschutMimetas BV, J.H. Oortweg 19, 2333 CH, Leiden, The Netherlands.
Benjamin SmithBiogen, 225 Binney Street, Cambridge, MA, 02142, USA.
Remko van VughtMimetas BV, J.H. Oortweg 19, 2333 CH, Leiden, The Netherlands.
Fumitaka ShimizuYamaguchi University Graduate School of Medicine, Minamikogushi, Ube, Yamaguchi, 7558505, Japan.
Yasuteru SanoYamaguchi University Graduate School of Medicine, Minamikogushi, Ube, Yamaguchi, 7558505, Japan.
Takashi KandaYamaguchi University Graduate School of Medicine, Minamikogushi, Ube, Yamaguchi, 7558505, Japan.
Graham MarshBiogen, 225 Binney Street, Cambridge, MA, 02142, USA.
Sebastiaan J TrietschMimetas BV, J.H. Oortweg 19, 2333 CH, Leiden, The Netherlands.
Paul VultoMimetas BV, J.H. Oortweg 19, 2333 CH, Leiden, The Netherlands.
Henriëtte L LanzMimetas BV, J.H. Oortweg 19, 2333 CH, Leiden, The Netherlands.
Birgit ObermeierBiogen, 225 Binney Street, Cambridge, MA, 02142, USA.
Mimetas (Netherlands) · NLBiogen (United States) · USYamaguchi University · JP

Funding

Horizon 2020 667375Innovative Medicines Initiative 115975
6 · The paper itself

Abstract

backgroundReceptor-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.

methodsThe 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.

resultsThe perfused BBB on-a-chip model shows presence of adherens and tight junctions and severely limits the passage of a 20 kDa FITC-dextran dye. Penetration of the antibody targeting the human transferrin receptor (MEM-189) was markedly higher than penetration of the control antibody (apparent permeability of 2.9 × 10

conclusionsWe 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.

Indexed as

Lab-On-A-Chip DevicesAntibodiesAstrocytesBlood-Brain BarrierCapillary PermeabilityCell LineDrug Evaluation, PreclinicalEndothelial CellsHumansMicrofluidic Analytical TechniquesMicrovesselsModels, NeurologicalPericytesAntibodiesAntibody transcytosisBBBBlood–brain barrierMicrofluidicsOrgan-on-a-chip

Identifiers

PMID30165870
PMCPMC6117964
OpenAlexW2887138305

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.