Evidence map›Paper›PMID 31197168›Full record

ArticleNature communications2019

Hypoxia-enhanced Blood-Brain Barrier Chip recapitulates human barrier function and shuttling of drugs and antibodies.

Tae-Eun Park, Nur Mustafaoglu, Anna Herland, Ryan Hasselkus, Robert Mannix, Edward A FitzGerald, Rachelle Prantil-Baun, Alexander Watters, Olivier Henry, Maximilian Benz and 7 more

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

Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 314 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
314citing papers in PubMed, 1 pooled it
34.0field-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

314 citing papers in PubMed, 1 synthesis or guideline pooled it, 579 citations in OpenAlex.

  1. Pooled it
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  8. Article
  9. Signaling pathways regulating cardiac regeneration.Cell regeneration (London, England) · 2026
    Review
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  15. BBB-Permeable PROTACs: Where Do We Stand?ACS medicinal chemistry letters · 2026
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254 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

17 authors at 3 institutions in 3 countries.

Tae-Eun ParkWyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, 02115, USA.ORCID http://orcid.org/0000-0003-3979-5405
Nur MustafaogluWyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, 02115, USA.
Anna HerlandWyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, 02115, USA.
Ryan HasselkusWyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, 02115, USA.ORCID http://orcid.org/0000-0002-0710-8722
Robert MannixWyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, 02115, USA.
Edward A FitzGeraldWyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, 02115, USA.ORCID http://orcid.org/0000-0002-0603-1241
Rachelle Prantil-BaunWyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, 02115, USA.
Alexander WattersWyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, 02115, USA.
Olivier HenryWyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, 02115, USA.
Maximilian BenzWyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, 02115, USA.ORCID http://orcid.org/0000-0002-8295-4996
Henry SanchezWyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, 02115, USA.
Heather J McCreaDepartment of Neurosurgery, Boston Children's Hospital and Harvard Medical School, Boston, MA, 02115, USA.
Liliana Christova GoumnerovaDepartment of Neurosurgery, Boston Children's Hospital and Harvard Medical School, Boston, MA, 02115, USA.ORCID http://orcid.org/0000-0002-2662-719X
Hannah W SongDepartment of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, WI, 53706, USA.
Sean P PalecekDepartment of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, WI, 53706, USA.
Eric ShustaDepartment of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, WI, 53706, USA.
Donald E IngberWyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, 02115, USA. don.ingber@wyss.harvard.edu.ORCID http://orcid.org/0000-0002-4319-6520
Harvard University · USBoston Children's Hospital · USUniversity of Wisconsin–Madison · US

Funding

Knut och Alice Wallenbergs Stiftelse (Knut and Alice Wallenberg Foundation) WAF 2015-0178National Research Foundation of Korea (NRF) 2018K1A4A3A01063890National Research Foundation of Korea (NRF) NRF-2018R1A5A1024340United States Department of Defense | Defense Advanced Research Projects Agency (DARPA) W911NF-12-2-0036
6 · The paper itself

Abstract

The high selectivity of the human blood-brain barrier (BBB) restricts delivery of many pharmaceuticals and therapeutic antibodies to the central nervous system. Here, we describe an in vitro microfluidic organ-on-a-chip BBB model lined by induced pluripotent stem cell-derived human brain microvascular endothelium interfaced with primary human brain astrocytes and pericytes that recapitulates the high level of barrier function of the in vivo human BBB for at least one week in culture. The endothelium expresses high levels of tight junction proteins and functional efflux pumps, and it displays selective transcytosis of peptides and antibodies previously observed in vivo. Increased barrier functionality was accomplished using a developmentally-inspired induction protocol that includes a period of differentiation under hypoxic conditions. This enhanced BBB Chip may therefore represent a new in vitro tool for development and validation of delivery systems that transport drugs and therapeutic antibodies across the human BBB.

Indexed as

AntibodiesAstrocytesBlood-Brain BarrierDrug Delivery SystemsDrug Evaluation, PreclinicalEndothelial CellsEndothelium, VascularHumansLab-On-A-Chip DevicesMicrofluidicsMicrovesselsPericytesPermeabilityPluripotent Stem CellsPrimary Cell CultureAntibodies

Identifiers

PMID31197168
PMCPMC6565686
OpenAlexW2953383090

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.