Evidence map›Paper›PMID 26794306›Full record

ArticlePloS one2016

Novel Immortal Cell Lines Support Cellular Heterogeneity in the Human Annulus Fibrosus.

Guus G H van den Akker, Don A M Surtel, Andy Cremers, Stephen M Richardson, Judith A Hoyland, Lodewijk W van Rhijn, Jan Willem Voncken, Tim J M Welting

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
3.4field-weighted citation impact, top 8% 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

26 citing papers in PubMed, 41 citations in OpenAlex.

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  14. Single-cell RNA-sequencing atlas of bovine caudal intervertebral discs: Discovery of heterogeneous cell populations with distinct roles in homeostasis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021
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  20. Neonatal mouse intervertebral discs heal with restored function following herniation injury.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018
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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

8 authors at 2 institutions in 2 countries.

Guus G H van den AkkerDepartment of Orthopaedic Surgery, Maastricht University Medical Centre, Maastricht, the Netherlands.
Don A M SurtelDepartment of Orthopaedic Surgery, Maastricht University Medical Centre, Maastricht, the Netherlands.
Andy CremersDepartment of Orthopaedic Surgery, Maastricht University Medical Centre, Maastricht, the Netherlands.
Stephen M RichardsonCentre for Tissue Injury and Repair, Institute of Inflammation and Repair, The University of Manchester, Manchester, United Kingdom.
Judith A HoylandCentre for Tissue Injury and Repair, Institute of Inflammation and Repair, The University of Manchester, Manchester, United Kingdom.
Lodewijk W van RhijnDepartment of Orthopaedic Surgery, Maastricht University Medical Centre, Maastricht, the Netherlands.
Jan Willem VonckenDepartment of Molecular Genetics, Maastricht University Medical Centre, Maastricht, the Netherlands.
Tim J M WeltingDepartment of Orthopaedic Surgery, Maastricht University Medical Centre, Maastricht, the Netherlands.
Maastricht University Medical Centre · NLUniversity of Manchester · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionLoss of annulus fibrosus (AF) integrity predisposes to disc herniation and is associated with IVD degeneration. Successful implementation of biomedical intervention therapy requires in-depth knowledge of IVD cell biology. We recently generated unique clonal human nucleus pulposus (NP) cell lines. Recurring functional cellular phenotypes from independent donors provided pivotal evidence for cell heterogeneity in the mature human NP. In this study we aimed to generate and characterize immortal cell lines for the human AF from matched donors.

methodsNon-degenerate healthy disc material was obtained as surplus surgical material. AF cells were immortalized by simian virus Large T antigen (SV40LTAg) and human telomerase (hTERT) expression. Early passage cells and immortalized cell clones were characterized based on marker gene expression under standardized culturing and in the presence of Transforming Growth factor β (TGFβ).

resultsThe AF-specific expression signature included COL1A1, COL5A1, COL12A1, SFRP2 and was largely maintained in immortal AF cell lines. Remarkably, TGFβ induced rapid 3D sheet formation in a subgroup of AF clones. This phenotype was associated with inherent differences in Procollagen type I processing and maturation, and correlated with differential mRNA expression of Prolyl 4-hydroxylase alpha polypeptide 1 and 3 (P4HA1,3) and Lysyl oxidase (LOX) between clones and differential P4HA3 protein expression between AF cells in histological sections.

conclusionWe report for the first time the generation of representative human AF cell lines. Gene expression profile analysis and functional comparison of AF clones revealed variation between immortalized cells and suggests phenotypic heterogeneity in the human AF. Future characterization of AF cellular (sub-)populations aims to combine identification of additional specific AF marker genes and their biological relevance. Ultimately this knowledge will contribute to clinical application of cell-based technology in IVD repair.

Indexed as

ADAM ProteinsADAMTS ProteinsAdolescentBiomarkersCartilage Oligomeric Matrix ProteinCell Line, TransformedCollagen Type ICollagen Type I, alpha 1 ChainCollagen Type IICollagen Type VFemaleHumansIntervertebral DiscMaleMembrane ProteinsProcollagen-Proline DioxygenaseADAM ProteinsADAMTS17 protein, humanADAMTS ProteinsBiomarkersCartilage Oligomeric Matrix ProteinCOL2A1 protein, humanCOL5A1 protein, humanCollagen Type ICollagen Type I, alpha 1 ChainCollagen Type IICollagen Type VMembrane ProteinsP4HA3 protein, humanProcollagen-Proline DioxygenaseSecreted Frizzled-Related ProteinsSFRP2 protein, humanTransforming Growth Factor betaTransforming Growth Factor beta3TSP5 protein, human

Identifiers

PMID26794306
PMCPMC4721917
OpenAlexW2410260366

What OpenQuestion holds

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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.