Evidence map›Paper›PMID 27872050›Full record

ArticleCirculation research2017

Experimental, Systems, and Computational Approaches to Understanding the MicroRNA-Mediated Reparative Potential of Cardiac Progenitor Cell-Derived Exosomes From Pediatric Patients.

Udit Agarwal, Alex George, Srishti Bhutani, Shohini Ghosh-Choudhary, Joshua T Maxwell, Milton E Brown, Yash Mehta, Manu O Platt, Yaxuan Liang, Susmita Sahoo and 1 more

Erratum issuedOpen access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 111 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
111citing papers in PubMed, 4 pooled it
12.2field-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

111 citing papers in PubMed, 4 syntheses or guidelines pooled it, 163 citations in OpenAlex.

  1. Pooled it
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  16. Stem cells-derived exosomes as cardiac regenerative agents.International journal of cardiology. Heart & vasculature · 2024
    Review
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  18. Article
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51 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 1 institution in 1 country.

Udit AgarwalFrom the Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta (U.A., A.G., S.B., S.G.-C., J.T.M., M.E.B., Y.M., M.O.P., M.E.D.); Division of Cardiology, Emory University School of Medicine, Atlanta, GA (U.A., J.T.M., M.E.B., M.E.D.); Children's Heart Research and Outcomes Center, Emory University School of Medicine and Children's Healthcare of Atlanta, GA (M.E.D.); and Cardiovascular Research Center, Icahn School of Medicine, Mount Sinai, New York (Y.L., S.S.).
Alex GeorgeFrom the Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta (U.A., A.G., S.B., S.G.-C., J.T.M., M.E.B., Y.M., M.O.P., M.E.D.); Division of Cardiology, Emory University School of Medicine, Atlanta, GA (U.A., J.T.M., M.E.B., M.E.D.); Children's Heart Research and Outcomes Center, Emory University School of Medicine and Children's Healthcare of Atlanta, GA (M.E.D.); and Cardiovascular Research Center, Icahn School of Medicine, Mount Sinai, New York (Y.L., S.S.).
Srishti BhutaniFrom the Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta (U.A., A.G., S.B., S.G.-C., J.T.M., M.E.B., Y.M., M.O.P., M.E.D.); Division of Cardiology, Emory University School of Medicine, Atlanta, GA (U.A., J.T.M., M.E.B., M.E.D.); Children's Heart Research and Outcomes Center, Emory University School of Medicine and Children's Healthcare of Atlanta, GA (M.E.D.); and Cardiovascular Research Center, Icahn School of Medicine, Mount Sinai, New York (Y.L., S.S.).
Shohini Ghosh-ChoudharyFrom the Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta (U.A., A.G., S.B., S.G.-C., J.T.M., M.E.B., Y.M., M.O.P., M.E.D.); Division of Cardiology, Emory University School of Medicine, Atlanta, GA (U.A., J.T.M., M.E.B., M.E.D.); Children's Heart Research and Outcomes Center, Emory University School of Medicine and Children's Healthcare of Atlanta, GA (M.E.D.); and Cardiovascular Research Center, Icahn School of Medicine, Mount Sinai, New York (Y.L., S.S.).
Joshua T MaxwellFrom the Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta (U.A., A.G., S.B., S.G.-C., J.T.M., M.E.B., Y.M., M.O.P., M.E.D.); Division of Cardiology, Emory University School of Medicine, Atlanta, GA (U.A., J.T.M., M.E.B., M.E.D.); Children's Heart Research and Outcomes Center, Emory University School of Medicine and Children's Healthcare of Atlanta, GA (M.E.D.); and Cardiovascular Research Center, Icahn School of Medicine, Mount Sinai, New York (Y.L., S.S.).
Milton E BrownFrom the Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta (U.A., A.G., S.B., S.G.-C., J.T.M., M.E.B., Y.M., M.O.P., M.E.D.); Division of Cardiology, Emory University School of Medicine, Atlanta, GA (U.A., J.T.M., M.E.B., M.E.D.); Children's Heart Research and Outcomes Center, Emory University School of Medicine and Children's Healthcare of Atlanta, GA (M.E.D.); and Cardiovascular Research Center, Icahn School of Medicine, Mount Sinai, New York (Y.L., S.S.).
Yash MehtaFrom the Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta (U.A., A.G., S.B., S.G.-C., J.T.M., M.E.B., Y.M., M.O.P., M.E.D.); Division of Cardiology, Emory University School of Medicine, Atlanta, GA (U.A., J.T.M., M.E.B., M.E.D.); Children's Heart Research and Outcomes Center, Emory University School of Medicine and Children's Healthcare of Atlanta, GA (M.E.D.); and Cardiovascular Research Center, Icahn School of Medicine, Mount Sinai, New York (Y.L., S.S.).
Manu O PlattFrom the Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta (U.A., A.G., S.B., S.G.-C., J.T.M., M.E.B., Y.M., M.O.P., M.E.D.); Division of Cardiology, Emory University School of Medicine, Atlanta, GA (U.A., J.T.M., M.E.B., M.E.D.); Children's Heart Research and Outcomes Center, Emory University School of Medicine and Children's Healthcare of Atlanta, GA (M.E.D.); and Cardiovascular Research Center, Icahn School of Medicine, Mount Sinai, New York (Y.L., S.S.).
Yaxuan LiangFrom the Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta (U.A., A.G., S.B., S.G.-C., J.T.M., M.E.B., Y.M., M.O.P., M.E.D.); Division of Cardiology, Emory University School of Medicine, Atlanta, GA (U.A., J.T.M., M.E.B., M.E.D.); Children's Heart Research and Outcomes Center, Emory University School of Medicine and Children's Healthcare of Atlanta, GA (M.E.D.); and Cardiovascular Research Center, Icahn School of Medicine, Mount Sinai, New York (Y.L., S.S.).
Susmita SahooFrom the Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta (U.A., A.G., S.B., S.G.-C., J.T.M., M.E.B., Y.M., M.O.P., M.E.D.); Division of Cardiology, Emory University School of Medicine, Atlanta, GA (U.A., J.T.M., M.E.B., M.E.D.); Children's Heart Research and Outcomes Center, Emory University School of Medicine and Children's Healthcare of Atlanta, GA (M.E.D.); and Cardiovascular Research Center, Icahn School of Medicine, Mount Sinai, New York (Y.L., S.S.).
Michael E DavisFrom the Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta (U.A., A.G., S.B., S.G.-C., J.T.M., M.E.B., Y.M., M.O.P., M.E.D.); Division of Cardiology, Emory University School of Medicine, Atlanta, GA (U.A., J.T.M., M.E.B., M.E.D.); Children's Heart Research and Outcomes Center, Emory University School of Medicine and Children's Healthcare of Atlanta, GA (M.E.D.); and Cardiovascular Research Center, Icahn School of Medicine, Mount Sinai, New York (Y.L., S.S.). michael.davis@bme.emory.edu.
Emory University · US

Funding

Atlanta Clinical and Translational Science Institute (ACTSI) RenewalUL1TR000454 · NCATS · EMORY UNIVERSITY · PI STEPHENS, DAVID S · 2012 to 2016
$25.8M
Research Trainng in Academic CardiologyT32HL007745 · NHLBI · EMORY UNIVERSITY · PI TAYLOR, WILLIAM ROBERT · 1994 to 2023
$10.6M
Therapeutic Mechanisms of Human CD34 ExosomesR01HL124187 · NHLBI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI SAHOO, SUSMITA · 2014 to 2018
$2.1M
Dysregulated Adenosine Methylation of mRNA as a Novel Mechanism of Heart FailureR01HL140469 · NHLBI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI SAHOO, SUSMITA · 2018 to 2021
$1.7M
CPC Excosomes for Cardiac TherapyR56HL124380 · NHLBI · EMORY UNIVERSITY · PI DAVIS, MICHAEL E · 2014 to 2014
$436k
NCATS NIH HHS UL1 TR000454NHLBI NIH HHS R01 HL124187NHLBI NIH HHS R01 HL140469NHLBI NIH HHS R56 HL124380NHLBI NIH HHS T32 HL007745
6 · The paper itself

Abstract

rationaleStudies have demonstrated that exosomes can repair cardiac tissue post-myocardial infarction and recapitulate the benefits of cellular therapy.

objectiveWe evaluated the role of donor age and hypoxia of human pediatric cardiac progenitor cell (CPC)-derived exosomes in a rat model of ischemia-reperfusion injury. METHODS AND

resultsHuman CPCs from the right atrial appendages from children of different ages undergoing cardiac surgery for congenital heart defects were isolated and cultured under hypoxic or normoxic conditions. Exosomes were isolated from the culture-conditioned media and delivered to athymic rats after ischemia-reperfusion injury. Echocardiography at day 3 post-myocardial infarction suggested statistically improved function in neonatal hypoxic and neonatal normoxic groups compared with saline-treated controls. At 28 days post-myocardial infarction, exosomes derived from neonatal normoxia, neonatal hypoxia, infant hypoxia, and child hypoxia significantly improved cardiac function compared with those from saline-treated controls. Staining showed decreased fibrosis and improved angiogenesis in hypoxic groups compared with controls. Finally, using sequencing data, a computational model was generated to link microRNA levels to specific outcomes.

conclusionsCPC exosomes derived from neonates improved cardiac function independent of culture oxygen levels, whereas CPC exosomes from older children were not reparative unless subjected to hypoxic conditions. Cardiac functional improvements were associated with increased angiogenesis, reduced fibrosis, and improved hypertrophy, resulting in improved cardiac function; however, mechanisms for normoxic neonatal CPC exosomes improved function independent of those mechanisms. This is the first study of its kind demonstrating that donor age and oxygen content in the microenvironment significantly alter the efficacy of human CPC-derived exosomes.

Indexed as

Age FactorsAnimalsCell HypoxiaCells, CulturedChildChild, PreschoolComprehensionDouble-Blind MethodExosomesHumansInfantInfant, NewbornMicroRNAsMyocytes, CardiacRandom AllocationRatsMicroRNAscardiac progenitor cellsexosomemicroRNAmodelingsystems biology

Identifiers

PMID27872050
PMCPMC5315680
OpenAlexW2549520480

What OpenQuestion holds

Textmetadata
LicenceTDM
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.