Evidence map›Paper›PMID 33055246›Full record

ArticleScience translational medicine2020

Endothelial extracellular vesicles contain protective proteins and rescue ischemia-reperfusion injury in a human heart-on-chip.

Moran Yadid, Johan U Lind, Herdeline Ann M Ardoña, Sean P Sheehy, Lauren E Dickinson, Feyisayo Eweje, Maartje M C Bastings, Benjamin Pope, Blakely B O'Connor, Juerg R Straubhaar and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Science translational medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
84citing papers in PubMed, 1 pooled it
–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

84 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  8. Spiro-Linked Polyketides from Cultures ofJournal of natural products · 2026
    Article
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  20. Circulating Extracellular Vesicles in Cardiovascular Disease.International journal of molecular sciences · 2025
    Review

24 more citing papers are in PubMed but not listed here.

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

13 authors.

Moran YadidDisease Biophysics Group, John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.ORCID 0000-0003-2682-1707
Johan U LindDisease Biophysics Group, John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.ORCID 0000-0002-0358-3999
Herdeline Ann M ArdoñaDisease Biophysics Group, John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.ORCID 0000-0003-0640-1262
Sean P SheehyDisease Biophysics Group, John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.
Lauren E DickinsonDisease Biophysics Group, John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.ORCID 0000-0002-7358-0806
Feyisayo EwejeDisease Biophysics Group, John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.ORCID 0000-0001-7936-5384
Maartje M C BastingsWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.
Benjamin PopeDisease Biophysics Group, John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.ORCID 0000-0003-1847-9163
Blakely B O'ConnorDisease Biophysics Group, John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.ORCID 0000-0003-0636-9514
Juerg R StraubhaarFAS Division of Science, Harvard University, Cambridge, MA 02138, USA.ORCID 0000-0001-9246-3392
Bogdan BudnikFAS Division of Science, Harvard University, Cambridge, MA 02138, USA.ORCID 0000-0003-3622-2003
Andre G KleberBeth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
Kevin Kit ParkerDisease Biophysics Group, John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA. kkparker@seas.harvard.edu.ORCID 0000-0002-5968-7535

Funding

Multi-scale modeling of inherited pediatric cardiomyopathiesUH3HL141798 · NHLBI · HARVARD UNIVERSITY · PI PARKER, KEVIN KIT, PU, WILLIAM TSWENCHING · 2019 to 2021
$3.9M
Human Cardio-Pulmonary System on a ChipUH3TR000522 · NCATS · HARVARD MEDICAL SCHOOL · PI PARKER, KEVIN KIT · 2014 to 2016
$3.6M
Multi-scale modeling of inherited pediatric cardiomyopathiesUG3HL141798 · NHLBI · HARVARD UNIVERSITY · PI PARKER, KEVIN KIT, PU, WILLIAM TSWENCHING · 2017 to 2018
$2.6M
NCATS NIH HHS UH3 TR000522NHLBI NIH HHS UG3 HL141798NHLBI NIH HHS UH3 HL141798
6 · The paper itself

Abstract

Extracellular vesicles (EVs) derived from various stem cell sources induce cardioprotective effects during ischemia-reperfusion injury (IRI). These have been attributed mainly to the antiapoptotic, proangiogenic, microRNA (miRNA) cargo within the stem cell-derived EVs. However, the mechanisms of EV-mediated endothelial signaling to cardiomyocytes, as well as their therapeutic potential toward ischemic myocardial injury, are not clear. EV content beyond miRNA that may contribute to cardioprotection has not been fully illuminated. This study characterized the protein cargo of human vascular endothelial EVs (EEVs) to identify lead cardioactive proteins and assessed the effect of EEVs on human laminar cardiac tissues (hlCTs) exposed to IRI. We mapped the protein content of human vascular EEVs and identified proteins that were previously associated with cellular metabolism, redox state, and calcium handling, among other processes. Analysis of the protein landscape of human cardiomyocytes revealed corresponding modifications induced by EEV treatment. To assess their human-specific cardioprotection in vitro, we developed a human heart-on-a-chip IRI assay using human stem cell-derived, engineered cardiac tissues. We found that EEVs alleviated cardiac cell death as well as the loss in contractile capacity during and after simulated IRI in an uptake- and dose-dependent manner. Moreover, we found that EEVs increased the respiratory capacity of normoxic cardiomyocytes. These results suggest that vascular EEVs rescue hlCTs exposed to IRI possibly by supplementing injured myocytes with cargo that supports multiple metabolic and salvage pathways and therefore may serve as a multitargeted therapy for IRI.

Indexed as

Extracellular VesiclesMicroRNAsReperfusion InjuryApoptosisHumansMyocytes, CardiacMicroRNAs

Identifiers

PMID33055246
PMCPMC8969368

What OpenQuestion holds

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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.