Evidence map›Paper›PMID 34992271›Full record

ArticleNature biomedical engineering2022

Conditional immortalization of human atrial myocytes for the generation of in vitro models of atrial fibrillation.

Niels Harlaar, Sven O Dekker, Juan Zhang, Rebecca R Snabel, Marieke W Veldkamp, Arie O Verkerk, Carla Cofiño Fabres, Verena Schwach, Lente J S Lerink, Mathilde R Rivaud and 11 more

Open access · greenAbstract read
PubMed Publisher
In one paragraph

Article in Nature biomedical engineering, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 1 pooled it
3.8field-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

20 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.

  1. Pooled it
  2. Smart Optogenetics for Real-Time Automated Control of Cardiac Electrical Activity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
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  10. Towards Improved HumanBiomedicines · 2023
    Review
  11. Harnessing developmental cues for cardiomyocyte production.Development (Cambridge, England) · 2023
    Review
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  14. Review
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  20. How Functional Genomics Can Keep Pace With VUS Identification.Frontiers in cardiovascular medicine · 2022
    Review
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

21 authors at 6 institutions in 2 countries.

Niels HarlaarDepartment of Cardiology, Leiden University Medical Center, Leiden, the Netherlands.ORCID http://orcid.org/0000-0003-2790-8708
Sven O DekkerDepartment of Cardiology, Leiden University Medical Center, Leiden, the Netherlands.
Juan ZhangDepartment of Cardiology, Leiden University Medical Center, Leiden, the Netherlands.
Rebecca R SnabelDepartment of Molecular Developmental Biology, Radboud University, Nijmegen, the Netherlands.ORCID http://orcid.org/0000-0001-8053-1191
Marieke W VeldkampDepartment of Clinical and Experimental Cardiology, Amsterdam UMC, Amsterdam, the Netherlands.
Arie O VerkerkDepartment of Clinical and Experimental Cardiology, Amsterdam UMC, Amsterdam, the Netherlands.ORCID http://orcid.org/0000-0003-2140-834X
Carla Cofiño FabresApplied Stem Cell Technologies, University of Twente, Enschede, the Netherlands.
Verena SchwachApplied Stem Cell Technologies, University of Twente, Enschede, the Netherlands.
Lente J S LerinkDepartment of Cardiology, Leiden University Medical Center, Leiden, the Netherlands.
Mathilde R RivaudDepartment of Clinical and Experimental Cardiology, Amsterdam UMC, Amsterdam, the Netherlands.
Aat A MulderDepartment of Cell and Chemical Biology, Leiden University Medical Center, Leiden, the Netherlands.
Willem E CorverDepartment of Pathology, Leiden University Medical Center, Leiden, the Netherlands.
Marie José T H GoumansDepartment of Cell and Chemical Biology, Leiden University Medical Center, Leiden, the Netherlands.ORCID http://orcid.org/0000-0001-9344-6746
Dobromir DobrevInstitute of Pharmacology, University Duisburg-Essen, Essen, Germany.
Robert J M KlautzDepartment of Cardiothoracic Surgery, Leiden University Medical Center, Leiden, the Netherlands.
Martin J SchalijDepartment of Cardiology, Leiden University Medical Center, Leiden, the Netherlands.
Gert Jan C VeenstraDepartment of Molecular Developmental Biology, Radboud University, Nijmegen, the Netherlands.ORCID http://orcid.org/0000-0002-7787-4940
Robert PassierApplied Stem Cell Technologies, University of Twente, Enschede, the Netherlands.ORCID http://orcid.org/0000-0003-4312-9296
Thomas J van BrakelDepartment of Cardiothoracic Surgery, Leiden University Medical Center, Leiden, the Netherlands.
Daniël A Pijnappels *Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands.
Antoine A F de Vries *Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands. a.a.f.de_vries@lumc.nl.ORCID http://orcid.org/0000-0002-4787-7155
Leiden University Medical Center · NLUniversity of Twente · NLAmsterdam University Medical Centers · NLRadboud University Nijmegen · NLAmsterdam UMC Location University of Amsterdam · NLUniversity of Duisburg-Essen · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The lack of a scalable and robust source of well-differentiated human atrial myocytes constrains the development of in vitro models of atrial fibrillation (AF). Here we show that fully functional atrial myocytes can be generated and expanded one-quadrillion-fold via a conditional cell-immortalization method relying on lentiviral vectors and the doxycycline-controlled expression of a recombinant viral oncogene in human foetal atrial myocytes, and that the immortalized cells can be used to generate in vitro models of AF. The method generated 15 monoclonal cell lines with molecular, cellular and electrophysiological properties resembling those of primary atrial myocytes. Multicellular in vitro models of AF generated using the immortalized atrial myocytes displayed fibrillatory activity (with activation frequencies of 6-8 Hz, consistent with the clinical manifestation of AF), which could be terminated by the administration of clinically approved antiarrhythmic drugs. The conditional cell-immortalization method could be used to generate functional cell lines from other human parenchymal cells, for the development of in vitro models of human disease.

Indexed as

Atrial FibrillationAnti-Arrhythmia AgentsHeart AtriaHumansMyocytes, CardiacAnti-Arrhythmia Agents

Identifiers

PMID34992271
OpenAlexW4205782343

What OpenQuestion holds

Textmetadata
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.