Evidence map›Paper›PMID 33213497›Full record

ArticleMolecular neurodegeneration2020

An in vitro bioengineered model of the human arterial neurovascular unit to study neurodegenerative diseases.

Jerome Robert, Nicholas L Weilinger, Li-Ping Cao, Stefano Cataldi, Emily B Button, Sophie Stukas, Emma M Martin, Philip Seibler, Megan Gilmour, Tara M Caffrey and 5 more

Open access · goldAbstract read
In one paragraph

Article in Molecular neurodegeneration, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
0.7field-weighted citation impact, top 24% 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

12 citing papers in PubMed, 14 citations in OpenAlex.

  1. Review
  2. HumanBioactive materials · 2026
    Article
  3. Review
  4. Article
  5. Review
  6. Article
  7. Review
  8. Article
  9. Article
  10. Review
  11. Toward three-dimensionalNeural regeneration research · 2021
    Review
  12. Generation and validation ofSTAR protocols · 2021
    Article
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

15 authors at 4 institutions in 4 countries.

Jerome RobertDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada. jerome.robert@usz.ch.ORCID 0000-0002-2847-9362
Nicholas L WeilingerDjavad Mowafaghian Centre for Brain Health, University of British Columbia, 2215 Wesbrook Mall, Vancouver, British Columbia, V6T 1Z3, Canada.
Li-Ping CaoDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada.
Stefano CataldiCentre for Applied Neurogenetics, University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada.
Emily B ButtonDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada.
Sophie StukasDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada.
Emma M MartinDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada.
Philip SeiblerInstitute of Neurogenetics, University of Luebeck, 23562, Luebeck, Germany.
Megan GilmourDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada.
Tara M CaffreyDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada.
Elyn M RoweDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada.
Jianjia FanDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada.
Brian MacVicarDjavad Mowafaghian Centre for Brain Health, University of British Columbia, 2215 Wesbrook Mall, Vancouver, British Columbia, V6T 1Z3, Canada.
Matthew J FarrerCentre for Applied Neurogenetics, University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada.
Cheryl L WellingtonDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada. cheryl.wellington@ubc.ca.
Vancouver Coastal Health · CAUniversity of British Columbia · CAUniversity of British Columbia Hospital · CAUniversity of Lübeck · DE

Funding

CIHR FDN148397
6 · The paper itself

Abstract

introductionThe neurovascular unit (NVU) - the interaction between the neurons and the cerebrovasculature - is increasingly important to interrogate through human-based experimental models. Although advanced models of cerebral capillaries have been developed in the last decade, there is currently no in vitro 3-dimensional (3D) perfusible model of the human cortical arterial NVU.

methodWe used a tissue-engineering technique to develop a scaffold-directed, perfusible, 3D human NVU that is cultured in native-like flow conditions that mimics the anatomy and physiology of cortical penetrating arteries.

resultsThis system, composed of primary human vascular cells (endothelial cells, smooth muscle cells and astrocytes) and induced pluripotent stem cell (iPSC) derived neurons, demonstrates a physiological multilayer organization of the involved cell types. It reproduces key characteristics of cortical neurons and astrocytes and enables formation of a selective and functional endothelial barrier. We provide proof-of-principle data showing that this in vitro human arterial NVU may be suitable to study neurovascular components of neurodegenerative diseases such as Alzheimer's disease (AD), as endogenously produced phosphorylated tau and beta-amyloid accumulate in the model over time. Finally, neuronal and glial fluid biomarkers relevant to neurodegenerative diseases are measurable in our arterial NVU model.

conclusionThis model is a suitable research tool to investigate arterial NVU functions in healthy and disease states. Further, the design of the platform allows culture under native-like flow conditions for extended periods of time and yields sufficient tissue and media for downstream immunohistochemistry and biochemistry analyses.

Indexed as

Alzheimer DiseaseArteriesAstrocytesBlood-Brain BarrierCoculture TechniquesEndothelial CellsHumansInduced Pluripotent Stem CellsNeurodegenerative DiseasesNeurons

Identifiers

PMID33213497
PMCPMC7678181
OpenAlexW3105413407

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.