Evidence map›Paper›PMID 28743804›Full record

ArticleCirculation research2017

Paracrine Effects of the Pluripotent Stem Cell-Derived Cardiac Myocytes Salvage the Injured Myocardium.

Atsushi Tachibana, Michelle R Santoso, Morteza Mahmoudi, Praveen Shukla, Lei Wang, Mihoko Bennett, Andrew B Goldstone, Mouer Wang, Masahiro Fukushi, Antje D Ebert and 3 more

Open 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. Cited by 102 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
102citing papers in PubMed, 2 pooled it
18.4field-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

102 citing papers in PubMed, 2 syntheses or guidelines pooled it, 161 citations in OpenAlex.

  1. Pooled it
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  14. Pluripotent stem cell-based approaches for heart repair and the potential of genetic modifications.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
  15. Stem Cell Therapy in Ischemic Heart Failure.American journal of cardiovascular drugs : drugs, devices, and other interventions · 2025
    Review
  16. Article
  17. Article
  18. Review
  19. Article
  20. Article

42 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 at 2 institutions in 2 countries.

Atsushi TachibanaFrom the Division of Cardiovascular Medicine (A.T., M.R.S., M.M., P.S., L.W., M.W., A.D.E., E.R., P.C.Y.), Division of Neonatal and Developmental Medicine (M.B.), and Department of Cardiothoracic Surgery (A.B.G., Y.J.W.), Stanford University, CA; Department of Radiological Sciences, Tokyo Metropolitan University, Japan (A.T., M.F.); Department of Critical Care Medicine, 2nd Affiliated Hospital of Guangzhou University of Chinese Medicine, China (L.W.); Department of Cardiology and Pneumonology, Göttingen University Medical Center, Germany (A.D.E.); and German Center for Cardiovascular Research, Partner Site Göttingen, Germany (A.D.E.).
Michelle R SantosoFrom the Division of Cardiovascular Medicine (A.T., M.R.S., M.M., P.S., L.W., M.W., A.D.E., E.R., P.C.Y.), Division of Neonatal and Developmental Medicine (M.B.), and Department of Cardiothoracic Surgery (A.B.G., Y.J.W.), Stanford University, CA; Department of Radiological Sciences, Tokyo Metropolitan University, Japan (A.T., M.F.); Department of Critical Care Medicine, 2nd Affiliated Hospital of Guangzhou University of Chinese Medicine, China (L.W.); Department of Cardiology and Pneumonology, Göttingen University Medical Center, Germany (A.D.E.); and German Center for Cardiovascular Research, Partner Site Göttingen, Germany (A.D.E.).
Morteza MahmoudiFrom the Division of Cardiovascular Medicine (A.T., M.R.S., M.M., P.S., L.W., M.W., A.D.E., E.R., P.C.Y.), Division of Neonatal and Developmental Medicine (M.B.), and Department of Cardiothoracic Surgery (A.B.G., Y.J.W.), Stanford University, CA; Department of Radiological Sciences, Tokyo Metropolitan University, Japan (A.T., M.F.); Department of Critical Care Medicine, 2nd Affiliated Hospital of Guangzhou University of Chinese Medicine, China (L.W.); Department of Cardiology and Pneumonology, Göttingen University Medical Center, Germany (A.D.E.); and German Center for Cardiovascular Research, Partner Site Göttingen, Germany (A.D.E.).
Praveen ShuklaFrom the Division of Cardiovascular Medicine (A.T., M.R.S., M.M., P.S., L.W., M.W., A.D.E., E.R., P.C.Y.), Division of Neonatal and Developmental Medicine (M.B.), and Department of Cardiothoracic Surgery (A.B.G., Y.J.W.), Stanford University, CA; Department of Radiological Sciences, Tokyo Metropolitan University, Japan (A.T., M.F.); Department of Critical Care Medicine, 2nd Affiliated Hospital of Guangzhou University of Chinese Medicine, China (L.W.); Department of Cardiology and Pneumonology, Göttingen University Medical Center, Germany (A.D.E.); and German Center for Cardiovascular Research, Partner Site Göttingen, Germany (A.D.E.).
Lei WangFrom the Division of Cardiovascular Medicine (A.T., M.R.S., M.M., P.S., L.W., M.W., A.D.E., E.R., P.C.Y.), Division of Neonatal and Developmental Medicine (M.B.), and Department of Cardiothoracic Surgery (A.B.G., Y.J.W.), Stanford University, CA; Department of Radiological Sciences, Tokyo Metropolitan University, Japan (A.T., M.F.); Department of Critical Care Medicine, 2nd Affiliated Hospital of Guangzhou University of Chinese Medicine, China (L.W.); Department of Cardiology and Pneumonology, Göttingen University Medical Center, Germany (A.D.E.); and German Center for Cardiovascular Research, Partner Site Göttingen, Germany (A.D.E.).
Mihoko BennettFrom the Division of Cardiovascular Medicine (A.T., M.R.S., M.M., P.S., L.W., M.W., A.D.E., E.R., P.C.Y.), Division of Neonatal and Developmental Medicine (M.B.), and Department of Cardiothoracic Surgery (A.B.G., Y.J.W.), Stanford University, CA; Department of Radiological Sciences, Tokyo Metropolitan University, Japan (A.T., M.F.); Department of Critical Care Medicine, 2nd Affiliated Hospital of Guangzhou University of Chinese Medicine, China (L.W.); Department of Cardiology and Pneumonology, Göttingen University Medical Center, Germany (A.D.E.); and German Center for Cardiovascular Research, Partner Site Göttingen, Germany (A.D.E.).
Andrew B GoldstoneFrom the Division of Cardiovascular Medicine (A.T., M.R.S., M.M., P.S., L.W., M.W., A.D.E., E.R., P.C.Y.), Division of Neonatal and Developmental Medicine (M.B.), and Department of Cardiothoracic Surgery (A.B.G., Y.J.W.), Stanford University, CA; Department of Radiological Sciences, Tokyo Metropolitan University, Japan (A.T., M.F.); Department of Critical Care Medicine, 2nd Affiliated Hospital of Guangzhou University of Chinese Medicine, China (L.W.); Department of Cardiology and Pneumonology, Göttingen University Medical Center, Germany (A.D.E.); and German Center for Cardiovascular Research, Partner Site Göttingen, Germany (A.D.E.).
Mouer WangFrom the Division of Cardiovascular Medicine (A.T., M.R.S., M.M., P.S., L.W., M.W., A.D.E., E.R., P.C.Y.), Division of Neonatal and Developmental Medicine (M.B.), and Department of Cardiothoracic Surgery (A.B.G., Y.J.W.), Stanford University, CA; Department of Radiological Sciences, Tokyo Metropolitan University, Japan (A.T., M.F.); Department of Critical Care Medicine, 2nd Affiliated Hospital of Guangzhou University of Chinese Medicine, China (L.W.); Department of Cardiology and Pneumonology, Göttingen University Medical Center, Germany (A.D.E.); and German Center for Cardiovascular Research, Partner Site Göttingen, Germany (A.D.E.).
Masahiro FukushiFrom the Division of Cardiovascular Medicine (A.T., M.R.S., M.M., P.S., L.W., M.W., A.D.E., E.R., P.C.Y.), Division of Neonatal and Developmental Medicine (M.B.), and Department of Cardiothoracic Surgery (A.B.G., Y.J.W.), Stanford University, CA; Department of Radiological Sciences, Tokyo Metropolitan University, Japan (A.T., M.F.); Department of Critical Care Medicine, 2nd Affiliated Hospital of Guangzhou University of Chinese Medicine, China (L.W.); Department of Cardiology and Pneumonology, Göttingen University Medical Center, Germany (A.D.E.); and German Center for Cardiovascular Research, Partner Site Göttingen, Germany (A.D.E.).
Antje D EbertFrom the Division of Cardiovascular Medicine (A.T., M.R.S., M.M., P.S., L.W., M.W., A.D.E., E.R., P.C.Y.), Division of Neonatal and Developmental Medicine (M.B.), and Department of Cardiothoracic Surgery (A.B.G., Y.J.W.), Stanford University, CA; Department of Radiological Sciences, Tokyo Metropolitan University, Japan (A.T., M.F.); Department of Critical Care Medicine, 2nd Affiliated Hospital of Guangzhou University of Chinese Medicine, China (L.W.); Department of Cardiology and Pneumonology, Göttingen University Medical Center, Germany (A.D.E.); and German Center for Cardiovascular Research, Partner Site Göttingen, Germany (A.D.E.).
Y Joseph WooFrom the Division of Cardiovascular Medicine (A.T., M.R.S., M.M., P.S., L.W., M.W., A.D.E., E.R., P.C.Y.), Division of Neonatal and Developmental Medicine (M.B.), and Department of Cardiothoracic Surgery (A.B.G., Y.J.W.), Stanford University, CA; Department of Radiological Sciences, Tokyo Metropolitan University, Japan (A.T., M.F.); Department of Critical Care Medicine, 2nd Affiliated Hospital of Guangzhou University of Chinese Medicine, China (L.W.); Department of Cardiology and Pneumonology, Göttingen University Medical Center, Germany (A.D.E.); and German Center for Cardiovascular Research, Partner Site Göttingen, Germany (A.D.E.).
Eric RulifsonFrom the Division of Cardiovascular Medicine (A.T., M.R.S., M.M., P.S., L.W., M.W., A.D.E., E.R., P.C.Y.), Division of Neonatal and Developmental Medicine (M.B.), and Department of Cardiothoracic Surgery (A.B.G., Y.J.W.), Stanford University, CA; Department of Radiological Sciences, Tokyo Metropolitan University, Japan (A.T., M.F.); Department of Critical Care Medicine, 2nd Affiliated Hospital of Guangzhou University of Chinese Medicine, China (L.W.); Department of Cardiology and Pneumonology, Göttingen University Medical Center, Germany (A.D.E.); and German Center for Cardiovascular Research, Partner Site Göttingen, Germany (A.D.E.).
Phillip C YangFrom the Division of Cardiovascular Medicine (A.T., M.R.S., M.M., P.S., L.W., M.W., A.D.E., E.R., P.C.Y.), Division of Neonatal and Developmental Medicine (M.B.), and Department of Cardiothoracic Surgery (A.B.G., Y.J.W.), Stanford University, CA; Department of Radiological Sciences, Tokyo Metropolitan University, Japan (A.T., M.F.); Department of Critical Care Medicine, 2nd Affiliated Hospital of Guangzhou University of Chinese Medicine, China (L.W.); Department of Cardiology and Pneumonology, Göttingen University Medical Center, Germany (A.D.E.); and German Center for Cardiovascular Research, Partner Site Göttingen, Germany (A.D.E.). phillip@stanford.edu.
Tokyo Metropolitan University · JPFirst Affiliated Hospital of Guangzhou University of Chinese Medicine · CN

Funding

Cell Characterization and Imaging for Regenerative Therapies in Ischemic DiseasesUM1HL113456 · NHLBI · STANFORD UNIVERSITY · PI YANG, PHILLIP CHUNG-MING · 2012 to 2018
$3.3M
NHLBI NIH HHS UM1 HL113456
6 · The paper itself

Abstract

rationaleCardiac myocytes derived from pluripotent stem cells have demonstrated the potential to mitigate damage of the infarcted myocardium and improve left ventricular ejection fraction. However, the mechanism underlying the functional benefit is unclear.

objectiveTo evaluate whether the transplantation of cardiac-lineage differentiated derivatives enhance myocardial viability and restore left ventricular ejection fraction more effectively than undifferentiated pluripotent stem cells after a myocardial injury. Herein, we utilize novel multimodality evaluation of human embryonic stem cells (hESCs), hESC-derived cardiac myocytes (hCMs), human induced pluripotent stem cells (iPSCs), and iPSC-derived cardiac myocytes (iCMs) in a murine myocardial injury model. METHODS AND

resultsPermanent ligation of the left anterior descending coronary artery was induced in immunosuppressed mice. Intramyocardial injection was performed with (1) hESCs (n=9), (2) iPSCs (n=8), (3) hCMs (n=9), (4) iCMs (n=14), and (5) PBS control (n=10). Left ventricular ejection fraction and myocardial viability, measured by cardiac magnetic resonance imaging and manganese-enhanced magnetic resonance imaging, respectively, was significantly improved in hCM- and iCM-treated mice compared with pluripotent stem cell- or control-treated mice. Bioluminescence imaging revealed limited cell engraftment in all treated groups, suggesting that the cell secretions may underlie the repair mechanism. To determine the paracrine effects of the transplanted cells, cytokines from supernatants from all groups were assessed in vitro. Gene expression and immunohistochemistry analyses of the murine myocardium demonstrated significant upregulation of the promigratory, proangiogenic, and antiapoptotic targets in groups treated with cardiac lineage cells compared with pluripotent stem cell and control groups.

conclusionsThis study demonstrates that the cardiac phenotype of hCMs and iCMs salvages the injured myocardium effectively than undifferentiated stem cells through their differential paracrine effects.

Indexed as

AnimalsCell LineCells, CulturedCytokinesEmbryonic Stem CellsHumansInduced Pluripotent Stem CellsMiceMyocardial InfarctionMyocytes, CardiacParacrine CommunicationStem Cell TransplantationCytokinescell therapycytokinesmagnetic resonance imagingmanganesemyocardial infarctionpluripotent stem cells

Identifiers

PMID28743804
PMCPMC5783162
OpenAlexW2736437772

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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.