Evidence map›Paper›PMID 28585535›Full record

ArticleNature communications2017

Blood-brain-barrier spheroids as an in vitro screening platform for brain-penetrating agents.

Choi-Fong Cho, Justin M Wolfe, Colin M Fadzen, David Calligaris, Kalvis Hornburg, E Antonio Chiocca, Nathalie Y R Agar, Bradley L Pentelute, Sean E Lawler

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

Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 191 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
191citing papers in PubMed, 3 pooled it
11.5field-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

191 citing papers in PubMed, 3 syntheses or guidelines pooled it, 330 citations in OpenAlex.

  1. Pooled it
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  14. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026
    Review
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  18. HumanBioactive materials · 2026
    Article
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131 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

9 authors at 3 institutions in 1 country.

Choi-Fong ChoHarvey Cushing Neuro-Oncology Laboratories, Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Justin M WolfeDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Colin M FadzenDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
David CalligarisDepartment of Neurosurgery and Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Kalvis HornburgHarvey Cushing Neuro-Oncology Laboratories, Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
E Antonio ChioccaHarvey Cushing Neuro-Oncology Laboratories, Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Nathalie Y R AgarDepartment of Neurosurgery and Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Bradley L PenteluteDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Sean E LawlerHarvey Cushing Neuro-Oncology Laboratories, Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Brigham and Women's Hospital · USMassachusetts Institute of Technology · USHarvard University · US

Funding

Indirubins: novel anti-invasive and anti-angiogenic drugs for malignant gliomasR01CA166172 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI CHIOCCA, E. ANTONIO · 2013 to 2017
$1.8M
NCI NIH HHS R01 CA166172
6 · The paper itself

Abstract

Culture-based blood-brain barrier (BBB) models are crucial tools to enable rapid screening of brain-penetrating drugs. However, reproducibility of in vitro barrier properties and permeability remain as major challenges. Here, we report that self-assembling multicellular BBB spheroids display reproducible BBB features and functions. The spheroid core is comprised mainly of astrocytes, while brain endothelial cells and pericytes encase the surface, acting as a barrier that regulates transport of molecules. The spheroid surface exhibits high expression of tight junction proteins, VEGF-dependent permeability, efflux pump activity and receptor-mediated transcytosis of angiopep-2. In contrast, the transwell co-culture system displays comparatively low levels of BBB regulatory proteins, and is unable to discriminate between the transport of angiopep-2 and a control peptide. Finally, we have utilized the BBB spheroids to screen and identify BBB-penetrant cell-penetrating peptides (CPPs). This robust in vitro BBB model could serve as a valuable next-generation platform for expediting the development of CNS therapeutics.

Indexed as

AstrocytesBiological TransportBlood-Brain BarrierCells, CulturedClaudin-5Coculture TechniquesEndothelial CellsHumansModels, BiologicalPeptidesPericytesPermeabilitySpheroids, CellularTight JunctionsZonula Occludens-1 ProteinAngiopep-2Claudin-5CLDN5 protein, humanPeptidesTJP1 protein, humanZonula Occludens-1 Protein

Identifiers

PMID28585535
PMCPMC5467173
OpenAlexW2624368609

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.