Evidence map›Paper›PMID 31189484›Full record

ArticleFluids and barriers of the CNS2019

A perfusion bioreactor-based 3D model of the subarachnoid space based on a meningeal tissue construct.

Albert Neutzner, Laura Power, Markus Dürrenberger, Hendrik P N Scholl, Peter Meyer, Hanspeter E Killer, David Wendt, Corina Kohler

Open access · goldAbstract read
PubMed Full text at PMC Publisher
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 3 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 1 pooled it
0.9field-weighted citation impact, top 25% 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

3 citing papers in PubMed, 1 synthesis or guideline pooled it, 10 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. 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

8 authors at 3 institutions in 1 country.

Albert NeutznerDepartment of Biomedicine, University Hospital Basel & University Basel, Hebelstr. 20, 4031, Basel, Switzerland.
Laura PowerDepartment of Biomedicine, University Hospital Basel & University Basel, Hebelstr. 20, 4031, Basel, Switzerland.
Markus DürrenbergerSwiss Nanoscience Institute, University Basel, Klingelbergstr. 50, 4056, Basel, Switzerland.
Hendrik P N SchollDepartment of Ophthalmology, University Hospital Basel & University Basel, Mittlere Str. 91, 4056, Basel, Switzerland.
Peter MeyerDepartment of Ophthalmology, University Hospital Basel & University Basel, Mittlere Str. 91, 4056, Basel, Switzerland.
Hanspeter E KillerDepartment of Ophthalmology, Kantonsspital Aarau, Tellstrasse 25, 5001, Aarau, Switzerland.
David WendtDepartment of Biomedicine, University Hospital Basel & University Basel, Hebelstr. 20, 4031, Basel, Switzerland. David.Wendt@usb.ch.
Corina KohlerDepartment of Biomedicine, University Hospital Basel & University Basel, Hebelstr. 20, 4031, Basel, Switzerland. Corina.Kohler@unibas.ch.
University Hospital of Basel · CHKantonsspital Aarau · CHSwiss Nanoscience Institute

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAltered flow of cerebrospinal fluid (CSF) within the subarachnoid space (SAS) is connected to brain, but also optic nerve degenerative diseases. To overcome the lack of suitable in vitro models that faithfully recapitulate the intricate three-dimensional architecture, complex cellular interactions, and fluid dynamics within the SAS, we have developed a perfusion bioreactor-based 3D in vitro model using primary human meningothelial cells (MECs) to generate meningeal tissue constructs. We ultimately employed this model to evaluate the impact of impaired CSF flow as evidenced during optic nerve compartment syndrome on the transcriptomic landscape of MECs.

methodsPrimary human meningothelial cells (phMECs) were seeded and cultured on collagen scaffolds in a perfusion bioreactor to generate engineered meningeal tissue constructs. Engineered constructs were compared to human SAS and assessed for specific cell-cell interaction markers as well as for extracellular matrix proteins found in human meninges. Using the established model, meningeal tissue constructs were exposed to physiological and pathophysiological flow conditions simulating the impaired CSF flow associated with optic nerve compartment syndrome and RNA sequencing was performed.

resultsEngineered constructs displayed similar microarchitecture compared to human SAS with regards to pore size, geometry as well as interconnectivity. They stained positively for specific cell-cell interaction markers indicative of a functional meningeal tissue, as well as extracellular matrix proteins found in human meninges. Analysis by RNA sequencing revealed altered expression of genes associated with extracellular matrix remodeling, endo-lysosomal processing, and mitochondrial energy metabolism under pathophysiological flow conditions.

conclusionsAlterations of these biological processes may not only interfere with critical MEC functions impacting CSF and hence optic nerve homeostasis, but may likely alter SAS structure, thereby further impeding cerebrospinal fluid flow. Future studies based on the established 3D model will lead to new insights into the role of MECs in the pathogenesis of optic nerve but also brain degenerative diseases.

Indexed as

BioreactorsModels, BiologicalCells, CulturedHumansMeningesSubarachnoid SpaceTissue EngineeringBioreactorCerebrospinal fluidMeningothelial cellsOptic nerveOptic nerve compartment syndromeSubarachnoid space

Identifiers

PMID31189484
PMCPMC6563372
OpenAlexW2950908475

What OpenQuestion holds

Textmetadata
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 OpenQuestion graph.