Evidence map›Paper›PMID 30391800›Full record

ArticleBiomaterials2019

Human iPSC-derived blood-brain barrier microvessels: validation of barrier function and endothelial cell behavior.

Raleigh M Linville, Jackson G DeStefano, Matt B Sklar, Zinnia Xu, Alanna M Farrell, Max I Bogorad, Chengyan Chu, Piotr Walczak, Linzhao Cheng, Vasiliki Mahairaki and 3 more

Abstract read
In one paragraph

Article in Biomaterials, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 120 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
120citing papers in PubMed, 1 pooled it
–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

120 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
  3. Review
  4. Guidelines for evaluating endothelial function in vascular tissue.American journal of physiology. Heart and circulatory physiology · 2026
    Review
  5. Article
  6. Article
  7. Review
  8. Article
  9. Review
  10. Transport Across the Blood-Brain Barrier.Advances in experimental medicine and biology · 2026
    Review
  11. Article
  12. Engineered 3D immuno-glial-neurovascular human miBrain model.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Permeability Benchmarking: Guidelines for ComparingJournal of chemical information and modeling · 2025
    Review
  19. Review
  20. Review

60 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

13 authors.

Raleigh M LinvilleInstitute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD, United States; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Jackson G DeStefanoInstitute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD, United States; Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD, United States.
Matt B SklarInstitute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD, United States.
Zinnia XuInstitute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD, United States; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Alanna M FarrellInstitute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD, United States; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Max I BogoradInstitute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD, United States; Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD, United States.
Chengyan ChuDepartment of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Piotr WalczakDepartment of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Linzhao ChengInstitute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Vasiliki MahairakiInstitute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, United States; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Katharine A WhartenbyDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Peter A CalabresiDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Peter C SearsonInstitute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD, United States; Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD, United States. Electronic address: searson@jhu.edu.

Funding

T32: Predoctoral and Postdoctoral Training Program in Nanotechnology for Cancer ResearchT32CA153952 · NCI · JOHNS HOPKINS UNIVERSITY · PI Denis Wirtz · 2015 to 2026
$3.5M
Mechanisms of cerebrovascular barrier dysfunction caused by APP and PSEN1 mutations and amyloid beta exposureR01NS106008 · NINDS · JOHNS HOPKINS UNIVERSITY · PI SEARSON, PETER C · 2019 to 2023
$1.9M
Treatment of ALS based on transplantation of glial restricted progenitorsR01NS091110 · NINDS · JOHNS HOPKINS UNIVERSITY · PI WALCZAK, PIOTR · 2015 to 2019
$1.8M
An engineered platform for the study of metastasis (PQ #24)R01CA170629 · NCI · JOHNS HOPKINS UNIVERSITY · PI SEARSON, PETER C · 2012 to 2015
$1.3M
T-32 NIH Postdoctoral Training Program in Nanotechnology for Cancer Medicine NTCMT32CA130840 · NCI · JOHNS HOPKINS UNIVERSITY · PI WIRTZ, DENIS · 2008 to 2012
$1.2M
In vitro brain post-capillary venule model: A platform to investigate leukocyte infiltration for multiple sclerosis therapeutic applicationsF31NS097209 · NINDS · JOHNS HOPKINS UNIVERSITY · PI XU, ZINNIA S · 2017 to 2018
$77k
NCI NIH HHS R01 CA170629NCI NIH HHS T32 CA130840NCI NIH HHS T32 CA153952NINDS NIH HHS F31 NS097209NINDS NIH HHS R01 NS091110NINDS NIH HHS R01 NS106008
6 · The paper itself

Abstract

Microvessels of the blood-brain barrier (BBB) regulate transport into the brain. The highly specialized brain microvascular endothelial cells, a major component of the BBB, express tight junctions and efflux transporters which regulate paracellular and transcellular permeability. However, most existing models of BBB microvessels fail to exhibit physiological barrier function. Here, using (iPSC)-derived human brain microvascular endothelial cells (dhBMECs) within templated type I collagen channels we mimic the cylindrical geometry, cell-extracellular matrix interactions, and shear flow typical of human brain post-capillary venules. We characterize the structure and barrier function in comparison to non-brain-specific microvessels, and show that dhBMEC microvessels recapitulate physiologically low solute permeability and quiescent endothelial cell behavior. Transcellular permeability is increased two-fold using a clinically relevant dose of a p-glycoprotein inhibitor tariquidar, while paracellular permeability is increased using a bolus dose of hyperosmolar agent mannitol. Lastly, we show that our human BBB microvessels are responsive to inflammatory cytokines via upregulation of surface adhesion molecules and increased leukocyte adhesion, but no changes in permeability. Human iPSC-derived blood-brain barrier microvessels support quantitative analysis of barrier function and endothelial cell dynamics in quiescence and in response to biologically- and clinically-relevant perturbations.

Indexed as

Blood-Brain BarrierCapillary PermeabilityCell DifferentiationCell LineEndothelial CellsEquipment DesignHumansInduced Pluripotent Stem CellsMicrovesselsTissue EngineeringBlood-brain barrierBrain microvascular endothelial cellsInduced pluripotent stem cellsMicrovesselsPermeabilityTissue engineering

Identifiers

PMID30391800
PMCPMC6289621

What OpenQuestion holds

Textmetadata
LicenceTDM
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.