Evidence map›Paper›PMID 25904597›Full record

ArticleCirculation research2015

Embryonic stem cell-derived exosomes promote endogenous repair mechanisms and enhance cardiac function following myocardial infarction.

Mohsin Khan, Emily Nickoloff, Tatiana Abramova, Jennifer Johnson, Suresh Kumar Verma, Prasanna Krishnamurthy, Alexander Roy Mackie, Erin Vaughan, Venkata Naga Srikanth Garikipati, Cynthia Benedict and 11 more

Abstract 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 468 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
468citing papers in PubMed, 5 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

468 citing papers in PubMed, 5 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Review
  7. Review
  8. Article
  9. Article
  10. Review
  11. Review
  12. Review
  13. Review
  14. Review
  15. Review
  16. Review
  17. Review
  18. Review
  19. Young cardiac telocyte-derived exosomes rejuvenate aging hearts in rats.Frontiers in cell and developmental biology · 2026
    Article
  20. Review

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

21 authors.

Mohsin KhanFrom the Center for Translational Medicine (M.K., E.N., J.J., S.K.V., P.K., E.V., V.N.S.G., C.B., E.G., T.L., J.E., W.J.K.), Cardiovascular Research Center (S.R.H.), Department of Physiology (S.R.H.), and Department of Pharmacology (T.L., W.J.K., R.K.), Temple University School of Medicine, Philadelphia, PA; and Feinberg Cardiovascular Research Institute, Northwestern University, Chicago, IL (T.A., A.R.M., E.V., V.R., E.L., A.I., S.M., G.Q., R.K.).
Emily NickoloffFrom the Center for Translational Medicine (M.K., E.N., J.J., S.K.V., P.K., E.V., V.N.S.G., C.B., E.G., T.L., J.E., W.J.K.), Cardiovascular Research Center (S.R.H.), Department of Physiology (S.R.H.), and Department of Pharmacology (T.L., W.J.K., R.K.), Temple University School of Medicine, Philadelphia, PA; and Feinberg Cardiovascular Research Institute, Northwestern University, Chicago, IL (T.A., A.R.M., E.V., V.R., E.L., A.I., S.M., G.Q., R.K.).
Tatiana AbramovaFrom the Center for Translational Medicine (M.K., E.N., J.J., S.K.V., P.K., E.V., V.N.S.G., C.B., E.G., T.L., J.E., W.J.K.), Cardiovascular Research Center (S.R.H.), Department of Physiology (S.R.H.), and Department of Pharmacology (T.L., W.J.K., R.K.), Temple University School of Medicine, Philadelphia, PA; and Feinberg Cardiovascular Research Institute, Northwestern University, Chicago, IL (T.A., A.R.M., E.V., V.R., E.L., A.I., S.M., G.Q., R.K.).
Jennifer JohnsonFrom the Center for Translational Medicine (M.K., E.N., J.J., S.K.V., P.K., E.V., V.N.S.G., C.B., E.G., T.L., J.E., W.J.K.), Cardiovascular Research Center (S.R.H.), Department of Physiology (S.R.H.), and Department of Pharmacology (T.L., W.J.K., R.K.), Temple University School of Medicine, Philadelphia, PA; and Feinberg Cardiovascular Research Institute, Northwestern University, Chicago, IL (T.A., A.R.M., E.V., V.R., E.L., A.I., S.M., G.Q., R.K.).
Suresh Kumar VermaFrom the Center for Translational Medicine (M.K., E.N., J.J., S.K.V., P.K., E.V., V.N.S.G., C.B., E.G., T.L., J.E., W.J.K.), Cardiovascular Research Center (S.R.H.), Department of Physiology (S.R.H.), and Department of Pharmacology (T.L., W.J.K., R.K.), Temple University School of Medicine, Philadelphia, PA; and Feinberg Cardiovascular Research Institute, Northwestern University, Chicago, IL (T.A., A.R.M., E.V., V.R., E.L., A.I., S.M., G.Q., R.K.).
Prasanna KrishnamurthyFrom the Center for Translational Medicine (M.K., E.N., J.J., S.K.V., P.K., E.V., V.N.S.G., C.B., E.G., T.L., J.E., W.J.K.), Cardiovascular Research Center (S.R.H.), Department of Physiology (S.R.H.), and Department of Pharmacology (T.L., W.J.K., R.K.), Temple University School of Medicine, Philadelphia, PA; and Feinberg Cardiovascular Research Institute, Northwestern University, Chicago, IL (T.A., A.R.M., E.V., V.R., E.L., A.I., S.M., G.Q., R.K.).
Alexander Roy MackieFrom the Center for Translational Medicine (M.K., E.N., J.J., S.K.V., P.K., E.V., V.N.S.G., C.B., E.G., T.L., J.E., W.J.K.), Cardiovascular Research Center (S.R.H.), Department of Physiology (S.R.H.), and Department of Pharmacology (T.L., W.J.K., R.K.), Temple University School of Medicine, Philadelphia, PA; and Feinberg Cardiovascular Research Institute, Northwestern University, Chicago, IL (T.A., A.R.M., E.V., V.R., E.L., A.I., S.M., G.Q., R.K.).
Erin VaughanFrom the Center for Translational Medicine (M.K., E.N., J.J., S.K.V., P.K., E.V., V.N.S.G., C.B., E.G., T.L., J.E., W.J.K.), Cardiovascular Research Center (S.R.H.), Department of Physiology (S.R.H.), and Department of Pharmacology (T.L., W.J.K., R.K.), Temple University School of Medicine, Philadelphia, PA; and Feinberg Cardiovascular Research Institute, Northwestern University, Chicago, IL (T.A., A.R.M., E.V., V.R., E.L., A.I., S.M., G.Q., R.K.).
Venkata Naga Srikanth GarikipatiFrom the Center for Translational Medicine (M.K., E.N., J.J., S.K.V., P.K., E.V., V.N.S.G., C.B., E.G., T.L., J.E., W.J.K.), Cardiovascular Research Center (S.R.H.), Department of Physiology (S.R.H.), and Department of Pharmacology (T.L., W.J.K., R.K.), Temple University School of Medicine, Philadelphia, PA; and Feinberg Cardiovascular Research Institute, Northwestern University, Chicago, IL (T.A., A.R.M., E.V., V.R., E.L., A.I., S.M., G.Q., R.K.).
Cynthia BenedictFrom the Center for Translational Medicine (M.K., E.N., J.J., S.K.V., P.K., E.V., V.N.S.G., C.B., E.G., T.L., J.E., W.J.K.), Cardiovascular Research Center (S.R.H.), Department of Physiology (S.R.H.), and Department of Pharmacology (T.L., W.J.K., R.K.), Temple University School of Medicine, Philadelphia, PA; and Feinberg Cardiovascular Research Institute, Northwestern University, Chicago, IL (T.A., A.R.M., E.V., V.R., E.L., A.I., S.M., G.Q., R.K.).
Veronica RamirezFrom the Center for Translational Medicine (M.K., E.N., J.J., S.K.V., P.K., E.V., V.N.S.G., C.B., E.G., T.L., J.E., W.J.K.), Cardiovascular Research Center (S.R.H.), Department of Physiology (S.R.H.), and Department of Pharmacology (T.L., W.J.K., R.K.), Temple University School of Medicine, Philadelphia, PA; and Feinberg Cardiovascular Research Institute, Northwestern University, Chicago, IL (T.A., A.R.M., E.V., V.R., E.L., A.I., S.M., G.Q., R.K.).
Erin LambersFrom the Center for Translational Medicine (M.K., E.N., J.J., S.K.V., P.K., E.V., V.N.S.G., C.B., E.G., T.L., J.E., W.J.K.), Cardiovascular Research Center (S.R.H.), Department of Physiology (S.R.H.), and Department of Pharmacology (T.L., W.J.K., R.K.), Temple University School of Medicine, Philadelphia, PA; and Feinberg Cardiovascular Research Institute, Northwestern University, Chicago, IL (T.A., A.R.M., E.V., V.R., E.L., A.I., S.M., G.Q., R.K.).
Aiko ItoFrom the Center for Translational Medicine (M.K., E.N., J.J., S.K.V., P.K., E.V., V.N.S.G., C.B., E.G., T.L., J.E., W.J.K.), Cardiovascular Research Center (S.R.H.), Department of Physiology (S.R.H.), and Department of Pharmacology (T.L., W.J.K., R.K.), Temple University School of Medicine, Philadelphia, PA; and Feinberg Cardiovascular Research Institute, Northwestern University, Chicago, IL (T.A., A.R.M., E.V., V.R., E.L., A.I., S.M., G.Q., R.K.).
Erhe GaoFrom the Center for Translational Medicine (M.K., E.N., J.J., S.K.V., P.K., E.V., V.N.S.G., C.B., E.G., T.L., J.E., W.J.K.), Cardiovascular Research Center (S.R.H.), Department of Physiology (S.R.H.), and Department of Pharmacology (T.L., W.J.K., R.K.), Temple University School of Medicine, Philadelphia, PA; and Feinberg Cardiovascular Research Institute, Northwestern University, Chicago, IL (T.A., A.R.M., E.V., V.R., E.L., A.I., S.M., G.Q., R.K.).
Sol MisenerFrom the Center for Translational Medicine (M.K., E.N., J.J., S.K.V., P.K., E.V., V.N.S.G., C.B., E.G., T.L., J.E., W.J.K.), Cardiovascular Research Center (S.R.H.), Department of Physiology (S.R.H.), and Department of Pharmacology (T.L., W.J.K., R.K.), Temple University School of Medicine, Philadelphia, PA; and Feinberg Cardiovascular Research Institute, Northwestern University, Chicago, IL (T.A., A.R.M., E.V., V.R., E.L., A.I., S.M., G.Q., R.K.).
Timothy LuongoFrom the Center for Translational Medicine (M.K., E.N., J.J., S.K.V., P.K., E.V., V.N.S.G., C.B., E.G., T.L., J.E., W.J.K.), Cardiovascular Research Center (S.R.H.), Department of Physiology (S.R.H.), and Department of Pharmacology (T.L., W.J.K., R.K.), Temple University School of Medicine, Philadelphia, PA; and Feinberg Cardiovascular Research Institute, Northwestern University, Chicago, IL (T.A., A.R.M., E.V., V.R., E.L., A.I., S.M., G.Q., R.K.).
John ElrodFrom the Center for Translational Medicine (M.K., E.N., J.J., S.K.V., P.K., E.V., V.N.S.G., C.B., E.G., T.L., J.E., W.J.K.), Cardiovascular Research Center (S.R.H.), Department of Physiology (S.R.H.), and Department of Pharmacology (T.L., W.J.K., R.K.), Temple University School of Medicine, Philadelphia, PA; and Feinberg Cardiovascular Research Institute, Northwestern University, Chicago, IL (T.A., A.R.M., E.V., V.R., E.L., A.I., S.M., G.Q., R.K.).
Gangjian QinFrom the Center for Translational Medicine (M.K., E.N., J.J., S.K.V., P.K., E.V., V.N.S.G., C.B., E.G., T.L., J.E., W.J.K.), Cardiovascular Research Center (S.R.H.), Department of Physiology (S.R.H.), and Department of Pharmacology (T.L., W.J.K., R.K.), Temple University School of Medicine, Philadelphia, PA; and Feinberg Cardiovascular Research Institute, Northwestern University, Chicago, IL (T.A., A.R.M., E.V., V.R., E.L., A.I., S.M., G.Q., R.K.).
Steven R HouserFrom the Center for Translational Medicine (M.K., E.N., J.J., S.K.V., P.K., E.V., V.N.S.G., C.B., E.G., T.L., J.E., W.J.K.), Cardiovascular Research Center (S.R.H.), Department of Physiology (S.R.H.), and Department of Pharmacology (T.L., W.J.K., R.K.), Temple University School of Medicine, Philadelphia, PA; and Feinberg Cardiovascular Research Institute, Northwestern University, Chicago, IL (T.A., A.R.M., E.V., V.R., E.L., A.I., S.M., G.Q., R.K.).
Walter J KochFrom the Center for Translational Medicine (M.K., E.N., J.J., S.K.V., P.K., E.V., V.N.S.G., C.B., E.G., T.L., J.E., W.J.K.), Cardiovascular Research Center (S.R.H.), Department of Physiology (S.R.H.), and Department of Pharmacology (T.L., W.J.K., R.K.), Temple University School of Medicine, Philadelphia, PA; and Feinberg Cardiovascular Research Institute, Northwestern University, Chicago, IL (T.A., A.R.M., E.V., V.R., E.L., A.I., S.M., G.Q., R.K.).
Raj KishoreFrom the Center for Translational Medicine (M.K., E.N., J.J., S.K.V., P.K., E.V., V.N.S.G., C.B., E.G., T.L., J.E., W.J.K.), Cardiovascular Research Center (S.R.H.), Department of Physiology (S.R.H.), and Department of Pharmacology (T.L., W.J.K., R.K.), Temple University School of Medicine, Philadelphia, PA; and Feinberg Cardiovascular Research Institute, Northwestern University, Chicago, IL (T.A., A.R.M., E.V., V.R., E.L., A.I., S.M., G.Q., R.K.). raj.kishore@temple.edu.

Funding

PKC alpha as a translational target in Heart FailureP01HL108806 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI RABINOWITZ, JOSEPH E · 2012 to 2016
$11.3M
Small Animal Surgery and HistologyP01HL108795 · NHLBI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI LOSORDO, DOUGLAS W · 2011 to 2015
$10.7M
Project 3 Dysregulation of metabolic communication of oligodendrocytes and neurons by cocaine and TatP01DA037830 · NIDA · TEMPLE UNIV OF THE COMMONWEALTH · PI KHALILI, KAMEL · 2015 to 2019
$7.4M
TNF mRNA stability and restenosisR01HL091983 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI KISHORE, RAJ · 2009 to 2022
$5.3M
Therapeutic Angiogenesis in Vascular Medicine IVR01HL053354 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI KISHORE, RAJ · 1995 to 2015
$4.2M
Mechanisms of mitochondrial calcium exchange in heart failureR01HL123966 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI ELROD, JOHN WILLIAM · 2014 to 2018
$2.3M
Pluripotent cell-derived exosomes as mediators of myocardial regenerationR01HL126186 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI KISHORE, RAJ · 2015 to 2018
$1.6M
Novel approaches to ischemic tissue repairR01HL095874 · NHLBI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI KISHORE, RAJ · 2009 to 2012
$1.5M
Effect of chronic alcohol on ischemic injury and endothelial cellsR01HL105597 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI KISHORE, RAJ · 2011 to 2014
$1.5M
THERAPEUTIC ANGIOGENESIS IN VASCULAR MEDICINE IIR37HL053354 · NHLBI · CARITAS ST. ELIZABETH'S MEDICAL CENTER · PI ISNER, JEFFREY · 2000 to 2001
$726k
NHLBI NIH HHS HL053354NHLBI NIH HHS HL091983NHLBI NIH HHS HL095874NHLBI NIH HHS HL105597NHLBI NIH HHS HL108795NHLBI NIH HHS HL108806NHLBI NIH HHS P01 HL108795NHLBI NIH HHS P01 HL108806NHLBI NIH HHS R01 HL053354NHLBI NIH HHS R01 HL091983NHLBI NIH HHS R01 HL095874NHLBI NIH HHS R01 HL105597NHLBI NIH HHS R01 HL123966NHLBI NIH HHS R01 HL126186NHLBI NIH HHS R37 HL053354NIDA NIH HHS P01 DA037830
6 · The paper itself

Abstract

rationaleEmbryonic stem cells (ESCs) hold great promise for cardiac regeneration but are susceptible to various concerns. Recently, salutary effects of stem cells have been connected to exosome secretion. ESCs have the ability to produce exosomes, however, their effect in the context of the heart is unknown.

objectiveDetermine the effect of ESC-derived exosome for the repair of ischemic myocardium and whether c-kit(+) cardiac progenitor cells (CPCs) function can be enhanced with ESC exosomes. METHODS AND

resultsThis study demonstrates that mouse ESC-derived exosomes (mES Ex) possess ability to augment function in infarcted hearts. mES Ex enhanced neovascularization, cardiomyocyte survival, and reduced fibrosis post infarction consistent with resurgence of cardiac proliferative response. Importantly, mES Ex augmented CPC survival, proliferation, and cardiac commitment concurrent with increased c-kit(+) CPCs in vivo 8 weeks after in vivo transfer along with formation of bonafide new cardiomyocytes in the ischemic heart. miRNA array revealed significant enrichment of miR290-295 cluster and particularly miR-294 in ESC exosomes. The underlying basis for the beneficial effect of mES Ex was tied to delivery of ESC specific miR-294 to CPCs promoting increased survival, cell cycle progression, and proliferation.

conclusionsmES Ex provide a novel cell-free system that uses the immense regenerative power of ES cells while avoiding the risks associated with direct ES or ES-derived cell transplantation and risk of teratomas. ESC exosomes possess cardiac regeneration ability and modulate both cardiomyocyte and CPC-based repair programs in the heart.

Indexed as

AnimalsCell-Free SystemCell SurvivalCollagenDrug CombinationsEmbryonic Stem CellsExosomesFibroblastsFibrosisGene Expression Regulation, DevelopmentalHeart VentriclesHumansHuman Umbilical Vein Endothelial CellsInduced Pluripotent Stem CellsInjectionsLamininCollagenDrug CombinationsLamininmatrigelMicroRNAsProteoglycansembryonic stem cellsexosomesmicroRNAs

Identifiers

PMID25904597
PMCPMC4482130

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.