Evidence map›Paper›PMID 31142333›Full record

ArticleFluids and barriers of the CNS2019

The endo-lysosomal system of bEnd.3 and hCMEC/D3 brain endothelial cells.

Andrea E Toth, Simone S E Nielsen, Weronika Tomaka, N Joan Abbott, Morten S Nielsen

Open access · goldAbstract read
In one paragraph

Article in Fluids and barriers of the CNS, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
2.4field-weighted citation impact, top 12% 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

19 citing papers in PubMed, 41 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 2 institutions in 2 countries.

Andrea E TothDepartment of Biomedicine, Faculty of Health, Aarhus University, Ole Worms Allé 3, 8000, Aarhus, Denmark. toth@biomed.au.dk.ORCID http://orcid.org/0000-0001-6122-919X
Simone S E NielsenDepartment of Biomedicine, Faculty of Health, Aarhus University, Ole Worms Allé 3, 8000, Aarhus, Denmark.
Weronika TomakaDepartment of Biomedicine, Faculty of Health, Aarhus University, Ole Worms Allé 3, 8000, Aarhus, Denmark.
N Joan AbbottInstitute of Pharmaceutical Science, King's College London, 150 Stamford Street, SE1 9NH, London, UK.
Morten S NielsenDepartment of Biomedicine, Faculty of Health, Aarhus University, Ole Worms Allé 3, 8000, Aarhus, Denmark. mn@biomed.au.dk.
Aarhus University · DKKing's College London · GB

Funding

Lundbeckfonden 2013-14113
6 · The paper itself

Abstract

backgroundBrain endothelial cell-based in vitro models are among the most versatile tools in blood-brain barrier research for testing drug penetration to the central nervous system. Transcytosis of large pharmaceuticals across the brain capillary endothelium involves the complex endo-lysosomal system. This system consists of several types of vesicle, such as early, late and recycling endosomes, retromer-positive structures, and lysosomes. Since the endo-lysosomal system in endothelial cell lines of in vitro blood-brain barrier models has not been investigated in detail, our aim was to characterize this system in different models.

methodsFor the investigation, we have chosen two widely-used models for in vitro drug transport studies: the bEnd.3 mouse and the hCMEC/D3 human brain endothelial cell line. We compared the structures and attributes of their endo-lysosomal system to that of primary porcine brain endothelial cells.

resultsWe detected significant differences in the vesicular network regarding number, morphology, subcellular distribution and lysosomal activity. The retromer-positive vesicles of the primary cells were distinct in many ways from those of the cell lines. However, the cell lines showed higher lysosomal degradation activity than the primary cells. Additionally, the hCMEC/D3 possessed a strikingly unique ratio of recycling endosomes to late endosomes.

conclusionsTaken together our data identify differences in the trafficking network of brain endothelial cells, essentially mapping the endo-lysosomal system of in vitro blood-brain barrier models. This knowledge is valuable for planning the optimal route across the blood-brain barrier and advancing drug delivery to the brain.

Indexed as

AnimalsBlood-Brain BarrierBrainCell LineEndothelial CellsHumansLysosomesMiceSwinebEnd.3 mouse brain endothelial cell lineBlood–brain barrierEndo-lysosomal systemhCMEC/D3 human brain endothelial cell lineIntracellular traffickingLysosomesPrimary porcine brain endothelial cellVesicular transport

Identifiers

PMID31142333
PMCPMC6542060
OpenAlexW2947173839

What Socratic holds

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LicenceCC BY
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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 Socratic graph.