Evidence map›Paper›PMID 36333694›Full record

ArticleFluids and barriers of the CNS2022

Three-dimensional microenvironment regulates gene expression, function, and tight junction dynamics of iPSC-derived blood-brain barrier microvessels.

Raleigh M Linville, Matthew B Sklar, Gabrielle N Grifno, Renée F Nerenberg, Justin Zhou, Robert Ye, Jackson G DeStefano, Zhaobin Guo, Ria Jha, John J Jamieson and 2 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Fluids and barriers of the CNS, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
6.1field-weighted citation impact, top 3% 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

29 citing papers in PubMed, 71 citations in OpenAlex.

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  9. Brain vascular basement membrane: Comparison of human and mouse brain at the transcriptomic and proteomic levels.Matrix biology : journal of the International Society for Matrix Biology · 2025
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  18. Synergistic induction of blood-brain barrier properties.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  19. Review
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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

12 authors at 1 institution in 1 country.

Raleigh M LinvilleInstitute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD, USA. raleigh@jhu.edu.
Matthew B SklarInstitute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD, USA.
Gabrielle N GrifnoInstitute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD, USA.
Renée F NerenbergInstitute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD, USA.
Justin ZhouInstitute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD, USA.
Robert YeInstitute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD, USA.
Jackson G DeStefanoInstitute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD, USA.
Zhaobin GuoInstitute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD, USA.
Ria JhaInstitute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD, USA.
John J JamiesonInstitute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD, USA.
Nan ZhaoInstitute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD, USA.
Peter C SearsonInstitute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD, USA. searson@jhu.edu.
Johns Hopkins University · US

Funding

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
Defense Threat Reduction Agency HDTRA1-15-1-0046NIH HHS R01NS106008NINDS NIH HHS R01 NS106008
6 · The paper itself

Abstract

The blood-brain barrier (BBB) plays a pivotal role in brain health and disease. In the BBB, brain microvascular endothelial cells (BMECs) are connected by tight junctions which regulate paracellular transport, and express specialized transporter systems which regulate transcellular transport. However, existing in vitro models of the BBB display variable accuracy across a wide range of characteristics including gene/protein expression and barrier function. Here, we use an isogenic family of fluorescently-labeled iPSC-derived BMEC-like cells (iBMECs) and brain pericyte-like cells (iPCs) within two-dimensional confluent monolayers (2D) and three-dimensional (3D) tissue-engineered microvessels to explore how 3D microenvironment regulates gene expression and function of the in vitro BBB. We show that 3D microenvironment (shear stress, cell-ECM interactions, and cylindrical geometry) increases BBB phenotype and endothelial identity, and alters angiogenic and cytokine responses in synergy with pericyte co-culture. Tissue-engineered microvessels incorporating junction-labeled iBMECs enable study of the real-time dynamics of tight junctions during homeostasis and in response to physical and chemical perturbations.

Indexed as

Blood-Brain BarrierInduced Pluripotent Stem CellsBrainCell DifferentiationCells, CulturedEndothelial CellsGene ExpressionMicrovesselsTight JunctionsBlood–brain barrierBrain microvascular endothelial cellsGene expressionInduced pluripotent stem cellsThree-dimensional models

Identifiers

PMID36333694
PMCPMC9636829
OpenAlexW4308261378

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.