Evidence map›Paper›PMID 38928202›Full record

ArticleInternational journal of molecular sciences2024

Modeling of Blood-Brain Barrier (BBB) Dysfunction and Immune Cell Migration Using Human BBB-on-a-Chip for Drug Discovery Research.

Masato Ohbuchi, Mayu Shibuta, Kazuhiro Tetsuka, Haruna Sasaki-Iwaoka, Masayo Oishi, Fumitaka Shimizu, Yasuhisa Nagasaka

Abstract read
In one paragraph

Article in International journal of molecular sciences, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
–field-weighted citation impact
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

16 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. HumanBioactive materials · 2026
    Article
  5. Review
  6. Review
  7. Review
  8. Article
  9. Review
  10. Article
  11. Article
  12. Perspective of usingFrontiers in immunology · 2025
    Review
  13. Review
  14. 3DFrontiers in pharmacology · 2025
    Review
  15. Blood-Brain Barrier Disruption in Neuroimmunological Disease.International journal of molecular sciences · 2024
    Review
  16. Review
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

7 authors.

Masato OhbuchiApplied Research & Operations, Astellas Pharma Inc., Tsukuba 305-8585, Ibaraki, Japan.
Mayu ShibutaApplied Research & Operations, Astellas Pharma Inc., Tsukuba 305-8585, Ibaraki, Japan.
Kazuhiro TetsukaApplied Research & Operations, Astellas Pharma Inc., Tsukuba 305-8585, Ibaraki, Japan.
Haruna Sasaki-IwaokaApplied Research & Operations, Astellas Pharma Inc., Tsukuba 305-8585, Ibaraki, Japan.
Masayo OishiApplied Research & Operations, Astellas Pharma Inc., Tsukuba 305-8585, Ibaraki, Japan.ORCID 0009-0009-0399-9968
Fumitaka ShimizuDepartment of Neurology and Clinical Neuroscience, Graduate School of Medicine, Yamaguchi University, Ube 755-8505, Yamaguchi, Japan.ORCID 0000-0003-4163-2939
Yasuhisa NagasakaApplied Research & Operations, Astellas Pharma Inc., Tsukuba 305-8585, Ibaraki, Japan.

Funding

Astellas Pharma (Japan) This work was funded by Astellas Pharma Inc.
6 · The paper itself

Abstract

Blood-brain barrier (BBB) dysfunction is a key feature in neuroimmunological and neurodegenerative diseases. In this study, we developed a microfluidic human BBB-on-a-chip to model barrier dysfunction and immune cell migration using immortalized TY10 brain endothelial cells, pericytes, and astrocytes. It was found that immortalized TY10 brain endothelial cells developed a microvascular structure under flow. Pericytes were localized on the basal side surrounding the TY10 microvascular structure, showing an in vivo-like structure. Barrier integrity increased under co-culture with pericytes. In addition, both ethylenediaminetetraacetic acid (EDTA) and anti-Claudin-5 (CLDN5) neutralizing antibody caused a decrease in the transendothelial electrical resistance (TEER). EDTA caused the leakage of 20 kDa dextran, suggesting different effects on the BBB based on the mechanism of action, whereas anti-CLDN5 antibody did not cause leakage. In the tri-culture model, human T cells migrated through endothelial vessels towards basal C-X-C motif chemokine ligand 12 (CXCL12). The live-imaging analysis confirmed the extravasation of fluorescence-labelled T cells in a CXCL12-concentration- and time-dependent manner. Our BBB model had an in vivo-like structure and successfully represented barrier dysfunction and transendothelial T cell migration. In addition, our study suggests that the inhibition of CLDN5 attenuates the BBB in humans. This platform has various potential uses in relation to the BBB in both drug discovery research and in elucidating the mechanisms of central nervous system diseases.

Indexed as

Blood-Brain BarrierCell MovementEndothelial CellsLab-On-A-Chip DevicesAstrocytesChemokine CXCL12Claudin-5Coculture TechniquesDrug DiscoveryHumansPericytesT-LymphocytesChemokine CXCL12Claudin-5barrier dysfunctionBBB-on-a-chipdrug discovery researchimmune cell migrationT cell

Identifiers

PMID38928202
PMCPMC11204321

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.