Evidence map›Paper›PMID 32673611›Full record

ArticleMicrovascular research2020

Three-dimensional induced pluripotent stem-cell models of human brain angiogenesis.

Raleigh M Linville, Diego Arevalo, Joanna C Maressa, Nan Zhao, Peter C Searson

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

Article in Microvascular research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
2.0field-weighted citation impact, top 13% 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

22 citing papers in PubMed, 36 citations in OpenAlex.

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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

5 authors at 1 institution in 1 country.

Raleigh M LinvilleInstitute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD, United States of America; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, United States of America.
Diego ArevaloInstitute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD, United States of America; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, United States of America.
Joanna C MaressaInstitute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD, United States of America; Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD, United States of America.
Nan ZhaoInstitute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD, United States of America.
Peter C SearsonInstitute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD, United States of America; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, United States of America; Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD, United States of America. Electronic address: searson@jhu.edu.
Johns Hopkins University · US

Funding

BIOMEDICAL ENGINEERING TRAINING PROGRAMT32GM007057 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI KANOLD, PATRICK O, KARCHIN, RACHEL · 1985 to 2023
$10.4M
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
NIGMS NIH HHS T32 GM007057NINDS NIH HHS R01 NS106008
6 · The paper itself

Abstract

During brain development, chemical cues released by developing neurons, cellular signaling with pericytes, and mechanical cues within the brain extracellular matrix (ECM) promote angiogenesis of brain microvascular endothelial cells (BMECs). Angiogenesis is also associated with diseases of the brain due to pathological chemical, cellular, and mechanical signaling. Existing in vitro and in vivo models of brain angiogenesis have key limitations. Here, we develop a high-throughput in vitro blood-brain barrier (BBB) bead assay of brain angiogenesis utilizing 150 μm diameter beads coated with induced pluripotent stem-cell (iPSC)-derived human BMECs (dhBMECs). After embedding the beads within a 3D matrix, we introduce various chemical cues and extracellular matrix components to explore their effects on angiogenic behavior. Based on the results from the bead assay, we generate a multi-scale model of the human cerebrovasculature within perfusable three-dimensional tissue-engineered blood-brain barrier microvessels. A sprouting phenotype is optimized in confluent monolayers of dhBMECs using chemical treatment with vascular endothelial growth factor (VEGF) and wnt ligands, and the inclusion of pro-angiogenic ECM components. As a proof-of-principle that the bead angiogenesis assay can be applied to study pathological angiogenesis, we show that oxidative stress can exert concentration-dependent effects on angiogenesis. Finally, we demonstrate the formation of a hierarchical microvascular model of the human blood-brain barrier displaying key structural hallmarks. We develop two in vitro models of brain angiogenesis: the BBB bead assay and the tissue-engineered BBB microvessel model. These platforms provide a tool kit for studies of physiological and pathological brain angiogenesis, with key advantages over existing two-dimensional models.

Indexed as

Cell DifferentiationNeovascularization, PhysiologicAngiogenesis Inducing AgentsBlood-Brain BarrierBrainCell Culture TechniquesCells, CulturedEndothelial CellsExtracellular MatrixHumansInduced Pluripotent Stem CellsModels, CardiovascularNeovascularization, PathologicOxidative StressPhenotypeWnt Signaling PathwayAngiogenesis Inducing AgentsBlood-brain barrierBrain angiogenesisBrain capillariesBrain microvascular endothelial cellsInduced pluripotent stem cellsMicrovascular tissue engineering

Identifiers

PMID32673611
PMCPMC7572715
OpenAlexW3042870380

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.