Evidence map›Paper›PMID 33599250›Full record

ArticleCardiovascular research2022

Regenerative potential of epicardium-derived extracellular vesicles mediated by conserved miRNA transfer.

Cristina Villa Del Campo, Norman Y Liaw, Mala Gunadasa-Rohling, Moritz Matthaei, Luca Braga, Tahnee Kennedy, Gabriela Salinas, Niels Voigt, Mauro Giacca, Wolfram-Hubertus Zimmermann and 1 more

Open access · hybridAbstract read
In one paragraph

Article in Cardiovascular research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed, 1 pooled it
13.6field-weighted citation impact, top 1% 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

53 citing papers in PubMed, 1 synthesis or guideline pooled it, 79 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
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  5. Article
  6. Article
  7. Article
  8. Heart-derived endogenous stem cells.Molecular biology reports · 2025
    Review
  9. Article
  10. Article
  11. Review
  12. Review
  13. Review
  14. Review
  15. Extracellular vesicle therapeutics for cardiac repair.Journal of molecular and cellular cardiology · 2025
    Review
  16. Article
  17. mCellular & molecular biology letters · 2024
    Article
  18. Review
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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

11 authors at 4 institutions in 3 countries.

Cristina Villa Del CampoDepartment of Physiology, Anatomy and Genetics, British Heart Foundation, Oxbridge Centre of Regenerative Medicine, University of Oxford, Sherrington Building, Sherrington Rd, Oxford OX1 3PT, UK.
Norman Y LiawInstitute of Pharmacology and Toxicology, University Medical Center Göttingen, Robert-Koch-Str. 40, 37075 Göttingen, Germany.ORCID 0000-0001-7804-8133
Mala Gunadasa-RohlingDepartment of Physiology, Anatomy and Genetics, British Heart Foundation, Oxbridge Centre of Regenerative Medicine, University of Oxford, Sherrington Building, Sherrington Rd, Oxford OX1 3PT, UK.
Moritz MatthaeiInstitute of Pharmacology and Toxicology, University Medical Center Göttingen, Robert-Koch-Str. 40, 37075 Göttingen, Germany.
Luca BragaMolecular Medicine Laboratory, International Centre for Genetic Engineering and Biotechnology (ICGEB), Località Padriciano, 99, 34149 Trieste TS, Italy.
Tahnee KennedyDepartment of Physiology, Anatomy and Genetics, British Heart Foundation, Oxbridge Centre of Regenerative Medicine, University of Oxford, Sherrington Building, Sherrington Rd, Oxford OX1 3PT, UK.ORCID 0000-0002-5486-7289
Gabriela SalinasNGS- Integrative Genomics Core Unit (NIG), Institute of Human Genetics, University Medical Centre Göttingen (UMG), Robert-Koch-Str. 40, 37075 Göttingen, Germany.
Niels VoigtInstitute of Pharmacology and Toxicology, University Medical Center Göttingen, Robert-Koch-Str. 40, 37075 Göttingen, Germany.ORCID 0000-0001-8230-2341
Mauro GiaccaMolecular Medicine Laboratory, International Centre for Genetic Engineering and Biotechnology (ICGEB), Località Padriciano, 99, 34149 Trieste TS, Italy.ORCID 0000-0003-2927-7225
Wolfram-Hubertus ZimmermannInstitute of Pharmacology and Toxicology, University Medical Center Göttingen, Robert-Koch-Str. 40, 37075 Göttingen, Germany.ORCID 0000-0003-1190-4040
Paul Richard RileyDepartment of Physiology, Anatomy and Genetics, British Heart Foundation, Oxbridge Centre of Regenerative Medicine, University of Oxford, Sherrington Building, Sherrington Rd, Oxford OX1 3PT, UK.ORCID 0000-0002-9862-7332
British Heart Foundation · GBUniversitätsmedizin Göttingen · DEKing's College London · GBUniversity of Göttingen · DE

Funding

British Heart Foundation CH/11/1/28798British Heart Foundation RG/18/5/33532
6 · The paper itself

Abstract

aimsAfter a myocardial infarction, the adult human heart lacks sufficient regenerative capacity to restore lost tissue, leading to heart failure progression. Finding novel ways to reprogram adult cardiomyocytes into a regenerative state is a major therapeutic goal. The epicardium, the outermost layer of the heart, contributes cardiovascular cell types to the forming heart and is a source of trophic signals to promote heart muscle growth during embryonic development. The epicardium is also essential for heart regeneration in zebrafish and neonatal mice and can be reactivated after injury in adult hearts to improve outcome. A recently identified mechanism of cell-cell communication and signalling is that mediated by extracellular vesicles (EVs). Here, we aimed to investigate epicardial signalling via EV release in response to cardiac injury and as a means to optimize cardiac repair and regeneration. METHODS AND

resultsWe isolated epicardial EVs from mouse and human sources and targeted the cardiomyocyte population. Epicardial EVs enhanced proliferation in H9C2 cells and in primary neonatal murine cardiomyocytes in vitro and promoted cell cycle re-entry when injected into the injured area of infarcted neonatal hearts. These EVs also enhanced regeneration in cryoinjured engineered human myocardium (EHM) as a novel model of human myocardial injury. Deep RNA-sequencing of epicardial EV cargo revealed conserved microRNAs (miRs) between human and mouse epicardial-derived exosomes, and the effects on cell cycle re-entry were recapitulated by administration of cargo miR-30a, miR-100, miR-27a, and miR-30e to human stem cell-derived cardiomyocytes and cryoinjured EHM constructs.

conclusionHere, we describe the first characterization of epicardial EV secretion, which can signal to promote proliferation of cardiomyocytes in infarcted mouse hearts and in a human model of myocardial injury, resulting in enhanced contractile function. Analysis of exosome cargo in mouse and human identified conserved pro-regenerative miRs, which in combination recapitulated the therapeutic effects of promoting cardiomyocyte proliferation.

Indexed as

Cell ProliferationRegenerationAnimalsAnimals, NewbornCell LineDisease Models, AnimalExtracellular VesiclesHuman Embryonic Stem CellsHumansMiceMice, Inbred C57BLMicroRNAsMyocardial ContractionMyocardial InfarctionMyocytes, CardiacParacrine CommunicationMicroRNAsEpicardiumExtracellular vesiclesFUCCIHuman engineered myocardiumMicroRNAMyocardial infarctionRegeneration

Identifiers

PMID33599250
PMCPMC8803084
OpenAlexW3132012205

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.