Evidence map›Paper›PMID 26375005›Full record

ArticleNature2015

Epicardial FSTL1 reconstitution regenerates the adult mammalian heart.

Ke Wei, Vahid Serpooshan, Cecilia Hurtado, Marta Diez-Cuñado, Mingming Zhao, Sonomi Maruyama, Wenhong Zhu, Giovanni Fajardo, Michela Noseda, Kazuto Nakamura and 17 more

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PubMed Full text at PMC Publisher
In one paragraph

Article in Nature, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 286 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
286citing papers in PubMed, 6 pooled it
22.7field-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

286 citing papers in PubMed, 6 syntheses or guidelines pooled it, 489 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Guideline
  7. Article
  8. Signaling pathways regulating cardiac regeneration.Cell regeneration (London, England) · 2026
    Review
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Journal of the American Heart Association · 2026
    Article
  15. Article
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  18. Review
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  20. Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

27 authors at 9 institutions in 4 countries.

Ke WeiDepartment of Bioengineering, University of California, San Diego, La Jolla, California 92037, USA.
Vahid SerpooshanStanford Cardiovascular Institute and Department of Pediatrics, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, California 94305, USA.
Cecilia HurtadoDepartment of Bioengineering, University of California, San Diego, La Jolla, California 92037, USA.
Marta Diez-CuñadoDepartment of Bioengineering, University of California, San Diego, La Jolla, California 92037, USA.
Mingming ZhaoStanford Cardiovascular Institute and Department of Pediatrics, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, California 94305, USA.
Sonomi MaruyamaWhitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
Wenhong ZhuDepartment of Bioengineering, University of California, San Diego, La Jolla, California 92037, USA.
Giovanni FajardoStanford Cardiovascular Institute and Department of Pediatrics, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, California 94305, USA.
Michela NosedaImperial College London, Faculty of Medicine, Imperial Centre for Translational and Experimental Medicine, Du Cane Road, London W12 0NN, UK.
Kazuto NakamuraWhitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
Xueying TianKey Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, and Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Qiaozhen LiuKey Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, and Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Andrew WangStanford Cardiovascular Institute and Department of Pediatrics, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, California 94305, USA.
Yuka MatsuuraStanford Cardiovascular Institute and Department of Pediatrics, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, California 94305, USA.
Paul BushwayDepartment of Bioengineering, University of California, San Diego, La Jolla, California 92037, USA.
Wenqing CaiDepartment of Bioengineering, University of California, San Diego, La Jolla, California 92037, USA.
Alex SavchenkoDepartment of Bioengineering, University of California, San Diego, La Jolla, California 92037, USA.
Morteza MahmoudiStanford Cardiovascular Institute and Department of Pediatrics, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, California 94305, USA.
Michael D SchneiderImperial College London, Faculty of Medicine, Imperial Centre for Translational and Experimental Medicine, Du Cane Road, London W12 0NN, UK.
Maurice J B van den HoffAcademic Medical Center. Dept Anatomy, Embryology and Physiology. Meibergdreef 15. 1105AZ Amsterdam, The Netherlands.
Manish J ButteStanford Cardiovascular Institute and Department of Pediatrics, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, California 94305, USA.
Phillip C YangStanford Cardiovascular Institute and Department of Pediatrics, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, California 94305, USA.
Kenneth WalshWhitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
Bin ZhouKey Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, and Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Daniel BernsteinStanford Cardiovascular Institute and Department of Pediatrics, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, California 94305, USA.
Mark MercolaDepartment of Bioengineering, University of California, San Diego, La Jolla, California 92037, USA.
Pilar Ruiz-LozanoStanford Cardiovascular Institute and Department of Pediatrics, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, California 94305, USA.
Stanford University · USCardiovascular Institute of the South · USUniversity of California, San Diego · USBoston University · USChinese Academy of Sciences · CNDiscovery Institute · USImperial College London · GBAcademic Medical Center · NLSanford Burnham Prebys Medical Discovery Institute · US

Funding

Tumor Microenvironment and Cancer ImmunologyP30CA030199 · NCI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI Michael Jackson · 1985 to 2026
$107.2M
Systems Biology CoreP01HL098053 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BODMER, ROLF · 2010 to 2014
$10.2M
GENETIC ABLATION OF EPICARDIAL FUNCTION IN THE MOUSER01HL065484 · NHLBI · UNIVERSITY OF CALIFORNIA SAN DIEGO · PI RUIZ-LOZANO, PILAR · 2002 to 2012
$3.7M
San Diego Skeletal Muscle Research CenterP30AR061303 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHEN, JU · 2011 to 2015
$3.3M
Cell Characterization and Imaging for Regenerative Therapies in Ischemic DiseasesUM1HL113456 · NHLBI · STANFORD UNIVERSITY · PI YANG, PHILLIP CHUNG-MING · 2012 to 2018
$3.3M
microRNAs and Integrative Control on Cardiopoiesis - CHANGE OF GRANTEE INSTITUTIOR01HL113601 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MERCOLA, MARK · 2012 to 2016
$2.2M
Myocardial Angiogenesis and CardioprotectionR01HL108176 · NHLBI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI MERCOLA, MARK · 2012 to 2015
$1.9M
Genetic Rescue of Retinoid-Induced DysfunctionR01HL086879 · NHLBI · STANFORD UNIVERSITY · PI RUIZ-LOZANO, PILAR · 2009 to 2013
$1.7M
Paracrine Regulation of Heart FailureR01HL116591 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI WALSH, KENNETH · 2013 to 2016
$1.6M
Influences of nanomechanical forces on T cellsR01GM110482 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BUTTE, MANISH J · 2014 to 2018
$1.6M
Mechanisms of T cell inhibitory pathwaysK08AI079268 · NIAID · STANFORD UNIVERSITY · PI BUTTE, MANISH J · 2009 to 2012
$531k
Genetic Ablation of Epicardial Function in the MouseR56HL065484 · NHLBI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI RUIZ-LOZANO, PILAR · 2007 to 2007
$478k
British Heart Foundation RG/08/007/25296British Heart Foundation RG/15/1/31165NCI NIH HHS P30 CA030199NHLBI NIH HHS 5UM1 HL113456NHLBI NIH HHS HL065484NHLBI NIH HHS HL108176NHLBI NIH HHS HL113601NHLBI NIH HHS HL116591NHLBI NIH HHS P01 HL098053NHLBI NIH HHS R01 HL065484NHLBI NIH HHS R01 HL086879NHLBI NIH HHS R01 HL108176NHLBI NIH HHS R01 HL113601NHLBI NIH HHS R01 HL116591NHLBI NIH HHS R56 HL065484NHLBI NIH HHS UM1 HL113456NIAID NIH HHS K08 AI079268NIAMS NIH HHS P30 AR061303NIGMS NIH HHS R01 GM110482
6 · The paper itself

Abstract

The elucidation of factors that activate the regeneration of the adult mammalian heart is of major scientific and therapeutic importance. Here we found that epicardial cells contain a potent cardiogenic activity identified as follistatin-like 1 (Fstl1). Epicardial Fstl1 declines following myocardial infarction and is replaced by myocardial expression. Myocardial Fstl1 does not promote regeneration, either basally or upon transgenic overexpression. Application of the human Fstl1 protein (FSTL1) via an epicardial patch stimulates cell cycle entry and division of pre-existing cardiomyocytes, improving cardiac function and survival in mouse and swine models of myocardial infarction. The data suggest that the loss of epicardial FSTL1 is a maladaptive response to injury, and that its restoration would be an effective way to reverse myocardial death and remodelling following myocardial infarction in humans.

Indexed as

RegenerationAnimalsCell CycleCell ProliferationCulture Media, ConditionedFemaleFollistatin-Related ProteinsHumansMaleMiceMyoblasts, CardiacMyocardial InfarctionMyocardiumMyocytes, CardiacPericardiumRatsCulture Media, ConditionedFollistatin-Related ProteinsFSTL1 protein, humanFstl1 protein, mouse

Identifiers

PMID26375005
PMCPMC4762253
OpenAlexW2157671340

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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.