Evidence map›Paper›PMID 24324277›Full record

ArticleStem cells translational medicine2014

Small molecule-mediated directed differentiation of human embryonic stem cells toward ventricular cardiomyocytes.

Ioannis Karakikes, Grant D Senyei, Jens Hansen, Chi-Wing Kong, Evren U Azeloglu, Francesca Stillitano, Deborah K Lieu, Jiaxian Wang, Lihuan Ren, Jean-Sebastien Hulot and 3 more

Open access · goldAbstract read
In one paragraph

Article in Stem cells translational medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.

0numbers the graph read from it
0cells of the map it votes in
87citing papers in PubMed
8.1field-weighted citation impact, top 2% 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

87 citing papers in PubMed, 174 citations in OpenAlex.

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27 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 3 institutions in 3 countries.

Ioannis KarakikesCardiovascular Research Center and Department of Pharmacology and Systems Therapeutics, Systems Biology Center, Icahn School of Medicine at Mount Sinai, New York, New York, USA; Stem Cell and Regenerative Medicine Consortium, Department of Physiology, LKS Faculty of Medicine, University of Hong Kong, Hong Kong.
Grant D Senyei
Jens Hansen
Chi-Wing Kong
Evren U Azeloglu
Francesca Stillitano
Deborah K Lieu
Jiaxian Wang
Lihuan Ren
Jean-Sebastien Hulot
Ravi Iyengar
Ronald A Li
Roger J Hajjar
Icahn School of Medicine at Mount Sinai · USChinese University of Hong Kong · CNUniversity of Hong Kong · HK

Funding

TRIP: Targeted Gene Therapy for the Treatment of Heart FailureP50HL112324 · NHLBI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI ASCHEIM, DEBORAH DAVIS, HAJJAR, ROGER J. · 2012 to 2014
$6.4M
C-TRIP: Targeted Gene Therapy for the Treatment of Heart Failure (P20)P20HL100396 · NHLBI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI HAJJAR, ROGER J. · 2010 to 2011
$1.7M
Gene Therapy with Cardiotropic Vectors for the Treatment of Heart FailureR01HL088434 · NHLBI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI HAJJAR, ROGER J. · 2010 to 2013
$1.7M
Regression of cardiac hypertrophyR01HL093183 · NHLBI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI HAJJAR, ROGER J. · 2009 to 2010
$1.1M
NHLBI NIH HHS HL088434NHLBI NIH HHS P20HL100396NHLBI NIH HHS P50 HL112324NHLBI NIH HHS R01 HL093183PHS HHS HHSN268201000045C
6 · The paper itself

Abstract

The generation of human ventricular cardiomyocytes from human embryonic stem cells and/or induced pluripotent stem cells could fulfill the demand for therapeutic applications and in vitro pharmacological research; however, the production of a homogeneous population of ventricular cardiomyocytes remains a major limitation. By combining small molecules and growth factors, we developed a fully chemically defined, directed differentiation system to generate ventricular-like cardiomyocytes (VCMs) from human embryonic stem cells and induced pluripotent stem cells with high efficiency and reproducibility. Molecular characterization revealed that the differentiation recapitulated the developmental steps of cardiovascular fate specification. Electrophysiological analyses further illustrated the generation of a highly enriched population of VCMs. These chemically induced VCMs exhibited the expected cardiac electrophysiological and calcium handling properties as well as the appropriate chronotropic responses to cardioactive compounds. In addition, using an integrated computational and experimental systems biology approach, we demonstrated that the modulation of the canonical Wnt pathway by the small molecule IWR-1 plays a key role in cardiomyocyte subtype specification. In summary, we developed a reproducible and efficient experimental platform that facilitates a chemical genetics-based interrogation of signaling pathways during cardiogenesis that bypasses the limitations of genetic approaches and provides a valuable source of ventricular cardiomyocytes for pharmacological screenings as well as cell replacement therapies.

Indexed as

Action PotentialsActivinsAntineoplastic AgentsBone Morphogenetic Protein 4CalciumCell DifferentiationCell LineCulture MediaEmbryonic Stem CellsHeart VentriclesHumansImidesInduced Pluripotent Stem CellsMyocytes, CardiacQuinolinesTranscriptomeactivin AActivinsAntineoplastic AgentsBMP4 protein, humanBone Morphogenetic Protein 4CalciumCulture MediaImidesIWR-1 compoundQuinolinesCardiacDifferentiationEmbryonic stem cellsPluripotent stem cells

Identifiers

PMID24324277
PMCPMC3902291
OpenAlexW2013384776

What OpenQuestion holds

Textmetadata
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.