Evidence map›Paper›PMID 34440833›Full record

ArticleCells2021

Generation, Characterization, and Application of Inducible Proliferative Adult Human Epicardium-Derived Cells.

Yang Ge, Anke M Smits, Jia Liu, Juan Zhang, Thomas J van Brakel, Marie José T H Goumans, Monique R M Jongbloed, Antoine A F de Vries

Open access · goldAbstract read
In one paragraph

Article in Cells, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed, 1 pooled it
0.8field-weighted citation impact, top 27% 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

9 citing papers in PubMed, 1 synthesis or guideline pooled it, 9 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Review
  8. Epicardial EMT and cardiac repair: an update.Stem cell research & therapy · 2024
    Review
  9. 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 1 institution in 2 countries.

Yang GeDepartment of Anatomy & Embryology, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, The Netherlands.ORCID 0000-0001-7667-5459
Anke M SmitsDepartment of Cell and Chemical Biology, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, The Netherlands.ORCID 0000-0002-2443-8547
Jia LiuDepartment of Cardiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.
Juan ZhangDepartment of Cardiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.
Thomas J van BrakelDepartment of Cardiothoracic Surgery, Leiden University Medical Center, Albinusdreef 2, 2333 ZC Leiden, The Netherlands.
Marie José T H GoumansDepartment of Cell and Chemical Biology, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, The Netherlands.ORCID 0000-0001-9344-6746
Monique R M JongbloedDepartment of Anatomy & Embryology, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, The Netherlands.ORCID 0000-0002-9132-0418
Antoine A F de VriesDepartment of Cardiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.ORCID 0000-0002-4787-7155
Leiden University Medical Center · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

rationaleIn recent decades, the great potential of human epicardium-derived cells (EPDCs) as an endogenous cell source for cardiac regeneration has been recognized. The limited availability and low proliferation capacity of primary human EPDCs and phenotypic differences between EPDCs obtained from different individuals hampers their reproducible use for experimental studies.

aimTo generate and characterize inducible proliferative adult human EPDCs for use in fundamental and applied research. METHODS AND

resultsInducible proliferation of human EPDCs was achieved by doxycycline-controlled expression of simian virus 40 large T antigen (LT) with a repressor-based lentiviral Tet-On system. In the presence of doxycycline, these inducible EPDCs (iEPDCs) displayed high and long-term proliferation capacity. After doxycycline removal, LT expression ceased and the iEPDCs regained their cuboidal epithelial morphology. Similar to primary EPDCs, iEPDCs underwent an epithelial-to-mesenchymal transition (EMT) after stimulation with transforming growth factor β3. This was confirmed by reverse transcription-quantitative polymerase chain reaction analysis of epithelial and mesenchymal marker gene expression and (immuno) cytochemical staining. Collagen gel-based cell invasion assays demonstrated that mesenchymal iEPDCs, like primary EPDCs, possess increased invasion and migration capacities as compared to their epithelial counterparts. Mesenchymal iEPDCs co-cultured with sympathetic ganglia stimulated neurite outgrowth similarly to primary EPDCs.

conclusionUsing an inducible LT expression system, inducible proliferative adult human EPDCs were generated displaying high proliferative capacity in the presence of doxycycline. These iEPDCs maintain essential epicardial characteristics with respect to morphology, EMT ability, and paracrine signaling following doxycycline removal. This renders iEPDCs a highly useful new in vitro model for studying human epicardial properties.

Indexed as

Antigens, Polyomavirus TransformingCell MovementCell ProliferationCells, CulturedCoculture TechniquesDoxycyclineEpithelial-Mesenchymal TransitionGanglia, SympatheticGenetic VectorsHumansModels, BiologicalNeuritesParacrine CommunicationPericardiumTransforming Growth Factor beta3Antigens, Polyomavirus TransformingDoxycyclineTransforming Growth Factor beta3conditional immortalizationepicardium-derived cells (EPDCs)epithelial-to-mesenchymal transition (EMT)simian virus 40 large T antigen (LT)

Identifiers

PMID34440833
PMCPMC8391799
OpenAlexW3191884665

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.