Evidence map›Paper›PMID 35411503›Full record

ArticlePharmaceutical research2022

Construction and Functional Evaluation of a Three-Dimensional Blood-Brain Barrier Model Equipped With Human Induced Pluripotent Stem Cell-Derived Brain Microvascular Endothelial Cells.

Toshiki Kurosawa, Daiki Sako, Yuma Tega, Yasuyuki Debori, Yumi Tomihara, Kazunobu Aoyama, Yoshiyuki Kubo, Nobuyuki Amano, Yoshiharu Deguchi

Erratum issuedOpen access · hybridAbstract read
In one paragraph

Article in Pharmaceutical research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
3.3field-weighted citation impact, top 6% 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, 35 citations in OpenAlex.

  1. Article
  2. Preclinical Models of Traumatic Brain Injury: Advances in In Vitro Models.Current neurology and neuroscience reports · 2026
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 1 institution in 1 country.

Toshiki KurosawaLaboratory of Drug Disposition and Pharmacokinetics, Faculty of Pharma-Sciences, Teikyo University, 2-11-1 Kaga, Itabashi, Tokyo, 173-8605, Japan.
Daiki SakoLaboratory of Drug Disposition and Pharmacokinetics, Faculty of Pharma-Sciences, Teikyo University, 2-11-1 Kaga, Itabashi, Tokyo, 173-8605, Japan.
Yuma TegaLaboratory of Drug Disposition and Pharmacokinetics, Faculty of Pharma-Sciences, Teikyo University, 2-11-1 Kaga, Itabashi, Tokyo, 173-8605, Japan.
Yasuyuki DeboriLaboratory of Drug Disposition and Pharmacokinetics, Faculty of Pharma-Sciences, Teikyo University, 2-11-1 Kaga, Itabashi, Tokyo, 173-8605, Japan.
Yumi TomiharaAxcelead Drug Discovery Partners Inc., 26-1, Muraoka-Higashi 2-chome Fujisawa, Kanagawa, 251-0012, Japan.
Kazunobu AoyamaAxcelead Drug Discovery Partners Inc., 26-1, Muraoka-Higashi 2-chome Fujisawa, Kanagawa, 251-0012, Japan.
Yoshiyuki KuboLaboratory of Drug Disposition and Pharmacokinetics, Faculty of Pharma-Sciences, Teikyo University, 2-11-1 Kaga, Itabashi, Tokyo, 173-8605, Japan.
Nobuyuki AmanoAxcelead Drug Discovery Partners Inc., 26-1, Muraoka-Higashi 2-chome Fujisawa, Kanagawa, 251-0012, Japan.
Yoshiharu DeguchiLaboratory of Drug Disposition and Pharmacokinetics, Faculty of Pharma-Sciences, Teikyo University, 2-11-1 Kaga, Itabashi, Tokyo, 173-8605, Japan. deguchi@pharm.teikyo-u.ac.jp.ORCID http://orcid.org/0000-0001-9904-9055
Teikyo University · JP

Funding

Japan Society for the Promotion of Science 19K07231Japan Society for the Promotion of Science 21K15321
6 · The paper itself

Abstract

purposeThe purpose of this study was to construct and validate an in vitro three-dimensional blood-brain barrier (3DBBB) model system equipped with brain microvascular endothelial cells derived from human induced pluripotent stem cells (hiPS-BMECs).

methodsThe 3D-BBB system was constructed by seeding hiPS-BMECs onto the capillary lane of a MIMETAS OrganoPlate RESULTS AND DISCUSSION: The expression of tight-junction proteins, including claudin-5 and ZO-1, was confirmed by immunohistochemistry. The permeability rate constant of lucifer yellow through hiPS-BMECs was undetectably low, indicating that paracellular transport is highly restricted by tight junctions in the 3D-BBB system. The mRNA expression levels of transporters and receptors in the 3D-BBB system differed from those in the 2D-culture system by 0.2- to 5.8-fold. The 3D-cultured hiPS-BMECs showed asymmetric transport of substrates of BCRP, CAT1 and LAT1 between the luminal (blood) and abluminal (brain) sides. Proton-coupled symport function of MCT1 was also confirmed.

conclusionThe 3D-BBB system constructed in this study mimics several important characteristics of the human BBB, and is expected to be a useful high-throughput evaluation tool in the development of CNS drugs.

Indexed as

Blood-Brain BarrierBrainEndothelial CellsInduced Pluripotent Stem CellsCells, CulturedHumansMembrane Transport ProteinsRNA, MessengerTight Junction ProteinsMembrane Transport ProteinsRNA, MessengerTight Junction Proteins3D cultureblood–brain barrierhuman iPS cellsorgan-on-a-chiptransporter

Identifiers

PMID35411503
PMCPMC9246774
OpenAlexW4223411185

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.