Evidence map›Paper›PMID 25344555›Full record

ArticleCirculation research2015

Identification of therapeutic covariant microRNA clusters in hypoxia-treated cardiac progenitor cell exosomes using systems biology.

Warren D Gray, Kristin M French, Shohini Ghosh-Choudhary, Joshua T Maxwell, Milton E Brown, Manu O Platt, Charles D Searles, Michael E Davis

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

Article in Circulation research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 256 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
256citing papers in PubMed, 3 pooled it
14.0field-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

256 citing papers in PubMed, 3 syntheses or guidelines pooled it, 372 citations in OpenAlex.

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  8. Endogenous Engineering Reprograms Extracellular Vesicles for Enhanced Therapeutic Function.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
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196 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Warren D GrayFrom the The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA (W.D.G., K.M.F., S.G.-C., J.T.M., M.E.B., M.O.P., M.E.D.); Division of Cardiology, Emory University School of Medicine, Atlanta, GA (W.D.G., C.D.S., M.E.D.); Atlanta Veterans Administration Medical Center, Decatur, GA (C.D.S.); and Emory+Children's Center for Cardiovascular Biology, Emory University School of Medicine and Children's Healthcare of Atlanta, GA (M.E.D.).
Kristin M FrenchFrom the The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA (W.D.G., K.M.F., S.G.-C., J.T.M., M.E.B., M.O.P., M.E.D.); Division of Cardiology, Emory University School of Medicine, Atlanta, GA (W.D.G., C.D.S., M.E.D.); Atlanta Veterans Administration Medical Center, Decatur, GA (C.D.S.); and Emory+Children's Center for Cardiovascular Biology, Emory University School of Medicine and Children's Healthcare of Atlanta, GA (M.E.D.).
Shohini Ghosh-ChoudharyFrom the The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA (W.D.G., K.M.F., S.G.-C., J.T.M., M.E.B., M.O.P., M.E.D.); Division of Cardiology, Emory University School of Medicine, Atlanta, GA (W.D.G., C.D.S., M.E.D.); Atlanta Veterans Administration Medical Center, Decatur, GA (C.D.S.); and Emory+Children's Center for Cardiovascular Biology, Emory University School of Medicine and Children's Healthcare of Atlanta, GA (M.E.D.).
Joshua T MaxwellFrom the The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA (W.D.G., K.M.F., S.G.-C., J.T.M., M.E.B., M.O.P., M.E.D.); Division of Cardiology, Emory University School of Medicine, Atlanta, GA (W.D.G., C.D.S., M.E.D.); Atlanta Veterans Administration Medical Center, Decatur, GA (C.D.S.); and Emory+Children's Center for Cardiovascular Biology, Emory University School of Medicine and Children's Healthcare of Atlanta, GA (M.E.D.).
Milton E BrownFrom the The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA (W.D.G., K.M.F., S.G.-C., J.T.M., M.E.B., M.O.P., M.E.D.); Division of Cardiology, Emory University School of Medicine, Atlanta, GA (W.D.G., C.D.S., M.E.D.); Atlanta Veterans Administration Medical Center, Decatur, GA (C.D.S.); and Emory+Children's Center for Cardiovascular Biology, Emory University School of Medicine and Children's Healthcare of Atlanta, GA (M.E.D.).
Manu O PlattFrom the The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA (W.D.G., K.M.F., S.G.-C., J.T.M., M.E.B., M.O.P., M.E.D.); Division of Cardiology, Emory University School of Medicine, Atlanta, GA (W.D.G., C.D.S., M.E.D.); Atlanta Veterans Administration Medical Center, Decatur, GA (C.D.S.); and Emory+Children's Center for Cardiovascular Biology, Emory University School of Medicine and Children's Healthcare of Atlanta, GA (M.E.D.).
Charles D SearlesFrom the The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA (W.D.G., K.M.F., S.G.-C., J.T.M., M.E.B., M.O.P., M.E.D.); Division of Cardiology, Emory University School of Medicine, Atlanta, GA (W.D.G., C.D.S., M.E.D.); Atlanta Veterans Administration Medical Center, Decatur, GA (C.D.S.); and Emory+Children's Center for Cardiovascular Biology, Emory University School of Medicine and Children's Healthcare of Atlanta, GA (M.E.D.).
Michael E DavisFrom the The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA (W.D.G., K.M.F., S.G.-C., J.T.M., M.E.B., M.O.P., M.E.D.); Division of Cardiology, Emory University School of Medicine, Atlanta, GA (W.D.G., C.D.S., M.E.D.); Atlanta Veterans Administration Medical Center, Decatur, GA (C.D.S.); and Emory+Children's Center for Cardiovascular Biology, Emory University School of Medicine and Children's Healthcare of Atlanta, GA (M.E.D.). michael.davis@bme.emory.edu.
United States Department of Veterans Affairs · USEmory University · US

Funding

CPC Excosomes for Cardiac TherapyR56HL124380 · NHLBI · EMORY UNIVERSITY · PI DAVIS, MICHAEL E · 2014 to 2014
$436k
NHLBI NIH HHS HHSN268201000043CNHLBI NIH HHS HL12438NHLBI NIH HHS R56 HL124380PHS HHS HHSN268201000043C
6 · The paper itself

Abstract

rationaleMyocardial infarction is a leading cause of death in developed nations, and there remains a need for cardiac therapeutic systems that mitigate tissue damage. Cardiac progenitor cells (CPCs) and other stem cell types are attractive candidates for treatment of myocardial infarction; however, the benefit of these cells may be as a result of paracrine effects.

objectiveWe tested the hypothesis that CPCs secrete proregenerative exosomes in response to hypoxic conditions. METHODS AND

resultsThe angiogenic and antifibrotic potential of secreted exosomes on cardiac endothelial cells and cardiac fibroblasts were assessed. We found that CPC exosomes secreted in response to hypoxia enhanced tube formation of endothelial cells and decreased profibrotic gene expression in TGF-β-stimulated fibroblasts, indicating that these exosomes possess therapeutic potential. Microarray analysis of exosomes secreted by hypoxic CPCs identified 11 miRNAs that were upregulated compared with exosomes secreted by CPCs grown under normoxic conditions. Principle component analysis was performed to identify miRNAs that were coregulated in response to distinct exosome-generating conditions. To investigate the cue-signal-response relationships of these miRNA clusters with a physiological outcome of tube formation or fibrotic gene expression, partial least squares regression analysis was applied. The importance of each up- or downregulated miRNA on physiological outcomes was determined. Finally, to validate the model, we delivered exosomes after ischemia-reperfusion injury. Exosomes from hypoxic CPCs improved cardiac function and reduced fibrosis.

conclusionsThese data provide a foundation for subsequent research of the use of exosomal miRNA and systems biology as therapeutic strategies for the damaged heart.

Indexed as

AnimalsAnimals, NewbornCell HypoxiaExosomesMicroRNAsMyocytes, CardiacRatsRats, Sprague-DawleyStem CellsSystems BiologyMicroRNAsexosomesmicroRNAsystems biology

Identifiers

PMID25344555
PMCPMC4338016
OpenAlexW2047107207

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.