Evidence map›Paper›PMID 27899163›Full record

ArticleStem cell research & therapy2016

Human fetal and adult epicardial-derived cells: a novel model to study their activation.

Asja T Moerkamp, Kirsten Lodder, Tessa van Herwaarden, Esther Dronkers, Calinda K E Dingenouts, Fredrik C Tengström, Thomas J van Brakel, Marie-José Goumans, Anke M Smits

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Article in Stem cell research & therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
–field-weighted citation impact
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

37 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Review
  6. Article
  7. Epicardium-myocardium crosstalk orchestrates heart development.Frontiers in cell and developmental biology · 2025
    Review
  8. The molecular mechanisms of cardiac development and related diseases.Signal transduction and targeted therapy · 2024
    Review
  9. Epicardial EMT and cardiac repair: an update.Stem cell research & therapy · 2024
    Review
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. Article
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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

9 authors.

Asja T MoerkampDepartment of Molecular Cell Biology, Leiden University Medical Center, P.O Box 9600, Postzone S-1-P, 2300RC, Leiden, The Netherlands.
Kirsten LodderDepartment of Molecular Cell Biology, Leiden University Medical Center, P.O Box 9600, Postzone S-1-P, 2300RC, Leiden, The Netherlands.
Tessa van HerwaardenDepartment of Molecular Cell Biology, Leiden University Medical Center, P.O Box 9600, Postzone S-1-P, 2300RC, Leiden, The Netherlands.
Esther DronkersDepartment of Molecular Cell Biology, Leiden University Medical Center, P.O Box 9600, Postzone S-1-P, 2300RC, Leiden, The Netherlands.
Calinda K E DingenoutsDepartment of Molecular Cell Biology, Leiden University Medical Center, P.O Box 9600, Postzone S-1-P, 2300RC, Leiden, The Netherlands.
Fredrik C TengströmDepartment of Molecular Cell Biology, Leiden University Medical Center, P.O Box 9600, Postzone S-1-P, 2300RC, Leiden, The Netherlands.
Thomas J van BrakelDepartment of Cardiothoracic Surgery, Leiden University Medical Center, P.O Box 9600, Postzone S-1-P, 2300RC, Leiden, The Netherlands.
Marie-José GoumansDepartment of Molecular Cell Biology, Leiden University Medical Center, P.O Box 9600, Postzone S-1-P, 2300RC, Leiden, The Netherlands. M.J.Goumans@lumc.nl.
Anke M SmitsDepartment of Molecular Cell Biology, Leiden University Medical Center, P.O Box 9600, Postzone S-1-P, 2300RC, Leiden, The Netherlands. A.M.Smits@lumc.nl.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe epicardium, a cell layer covering the heart, plays an important role during cardiogenesis providing cardiovascular cell types and instructive signals, but becomes quiescent during adulthood. Upon cardiac injury the epicardium is activated, which includes induction of a developmental gene program, epithelial-to-mesenchymal transition (EMT) and migration. However, the response of the adult epicardium is suboptimal compared to the active contribution of the fetal epicardium to heart development. To understand the therapeutic value of epicardial-derived cells (EPDCs), a direct comparison of fetal and adult sources is paramount. Such analysis has been hampered by the lack of appropriate culture systems.

methodsHuman fetal and adult EPDCs were isolated from cardiac specimens obtained after informed consent. EPDCs were cultured in the presence of an inhibitor of the TGFβ receptor ALK5. EMT was induced by stimulation with 1 ng/ml TGFβ. PCR, immunofluorescent staining, scratch assay, tube formation assay and RT

resultsIn this study, a novel protocol is presented that allows efficient isolation of human EPDCs from fetal and adult heart tissue. In vitro, EPDCs maintain epithelial characteristics and undergo EMT upon TGFβ stimulation. Although similar in several aspects, we observed important differences between fetal and adult EPDCs. Fetal and adult cells display equal migration abilities in their epithelial state. However, while TGFβ stimulation enhanced adult EPDC migration, it resulted in a reduced migration in fetal EPDCs. Matrigel assays revealed the ability of adult EPDCs to form tube-like structures, which was absent in fetal cells. Furthermore, we observed that fetal cells progress through EMT faster and undergo spontaneous EMT when TGFβ signaling is not suppressed, indicating that fetal EPDCs more rapidly respond to environmental changes.

conclusionsOur data suggest that fetal and adult EPDCs are in a different state of activation and that their phenotypic plasticity is determined by this activation state. This culture system allows us to establish the cues that determine epicardial activation, behavior, and plasticity and thereby optimize the adult response post-injury.

Indexed as

Cell MovementCells, CulturedCollagenDrug CombinationsEpithelial-Mesenchymal TransitionFetusHeartHumansLamininOrganogenesisPericardiumProteoglycansReceptors, Transforming Growth Factor betaCollagenDrug CombinationsLamininmatrigelProteoglycansReceptors, Transforming Growth Factor betaCardiac developmentEpicardiumEpithelial-to-mesenchymal transitionHuman EPDCsIn vitro modelTGFβ

Identifiers

PMID27899163
PMCPMC5129650

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Registered trials

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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.