Evidence map›Paper›PMID 27935037›Full record

ArticleJournal of neurochemistry2017

An isogenic blood-brain barrier model comprising brain endothelial cells, astrocytes, and neurons derived from human induced pluripotent stem cells.

Scott G Canfield, Matthew J Stebbins, Bethsymarie Soto Morales, Shusaku W Asai, Gad D Vatine, Clive N Svendsen, Sean P Palecek, Eric V Shusta

Abstract read
In one paragraph

Article in Journal of neurochemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 137 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
137citing papers in PubMed, 2 pooled it
14.2field-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

137 citing papers in PubMed, 2 syntheses or guidelines pooled it, 256 citations in OpenAlex.

  1. Pooled it
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  6. HumanBioactive materials · 2026
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77 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 2 countries.

Scott G CanfieldDepartment of Chemical and Biological Engineering, University of Wisconsin Madison, Madison, Wisconsin, USA.ORCID 0000-0003-1328-7365
Matthew J StebbinsDepartment of Chemical and Biological Engineering, University of Wisconsin Madison, Madison, Wisconsin, USA.
Bethsymarie Soto MoralesDepartment of Chemical and Biological Engineering, University of Wisconsin Madison, Madison, Wisconsin, USA.
Shusaku W AsaiDepartment of Chemical and Biological Engineering, University of Wisconsin Madison, Madison, Wisconsin, USA.
Gad D VatineCedars-Sinai Medical Center, Board of Governors Regenerative Medicine Institute, Los Angeles, California, USA.
Clive N SvendsenCedars-Sinai Medical Center, Board of Governors Regenerative Medicine Institute, Los Angeles, California, USA.
Sean P PalecekDepartment of Chemical and Biological Engineering, University of Wisconsin Madison, Madison, Wisconsin, USA.
Eric V ShustaDepartment of Chemical and Biological Engineering, University of Wisconsin Madison, Madison, Wisconsin, USA.
University of Wisconsin–Madison · USCedars-Sinai Medical Center · US

Funding

BIOTECHNOLOGY TRAINING PROGRAMT32GM008349 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI FOX, BRIAN G · 1989 to 2019
$22.5M
RXRalpha and PPARdelta Signaling as Novel Regulators of the Blood-Brain BarrierR01NS083688 · NINDS · UNIVERSITY OF WISCONSIN-MADISON · PI SHUSTA, ERIC V · 2013 to 2017
$1.9M
NIGMS NIH HHS T32 GM008349NINDS NIH HHS R01 NS083688
6 · The paper itself

Abstract

The blood-brain barrier (BBB) is critical in maintaining a physical and metabolic barrier between the blood and the brain. The BBB consists of brain microvascular endothelial cells (BMECs) that line the brain vasculature and combine with astrocytes, neurons and pericytes to form the neurovascular unit. We hypothesized that astrocytes and neurons generated from human-induced pluripotent stem cells (iPSCs) could induce BBB phenotypes in iPSC-derived BMECs, creating a robust multicellular human BBB model. To this end, iPSCs were used to form neural progenitor-like EZ-spheres, which were in turn differentiated to neurons and astrocytes, enabling facile neural cell generation. The iPSC-derived astrocytes and neurons induced barrier tightening in primary rat BMECs indicating their BBB inductive capacity. When co-cultured with human iPSC-derived BMECs, the iPSC-derived neurons and astrocytes significantly elevated trans-endothelial electrical resistance, reduced passive permeability, and improved tight junction continuity in the BMEC cell population, while p-glycoprotein efflux transporter activity was unchanged. A physiologically relevant neural cell mixture of one neuron: three astrocytes yielded optimal BMEC induction properties. Finally, an isogenic multicellular BBB model was successfully demonstrated employing BMECs, astrocytes, and neurons from the same donor iPSC source. It is anticipated that such an isogenic facsimile of the human BBB could have applications in furthering understanding the cellular interplay of the neurovascular unit in both healthy and diseased humans. Read the Editorial Highlight for this article on page 843.

Indexed as

3T3 CellsAnimalsAstrocytesBlood-Brain BarrierBrainCell DifferentiationCells, CulturedCoculture TechniquesEndothelial CellsEndothelium, VascularHumansInduced Pluripotent Stem CellsMaleMiceNeuronsRatsastrocytesblood-brain barrier modelneuronsneurovascular unitstem cells

Identifiers

PMID27935037
PMCPMC5339046
OpenAlexW2559974977

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.