Evidence map›Paper›PMID 22912385›Full record

ArticleCirculation research2012

Extracellular matrix promotes highly efficient cardiac differentiation of human pluripotent stem cells: the matrix sandwich method.

Jianhua Zhang, Matthew Klos, Gisela F Wilson, Amanda M Herman, Xiaojun Lian, Kunil K Raval, Matthew R Barron, Luqia Hou, Andrew G Soerens, Junying Yu and 6 more

Open access · bronzeAbstract read
In one paragraph

Article in Circulation research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 269 papers.

0numbers the graph read from it
0cells of the map it votes in
269citing papers in PubMed
45.2field-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

269 citing papers in PubMed, 453 citations in OpenAlex.

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  16. Environmental Cues Facilitate Maturation and Patterning of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2024
    Article
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209 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

16 authors at 5 institutions in 1 country.

Jianhua ZhangDepartment of Medicine, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA.
Matthew Klos
Gisela F Wilson
Amanda M Herman
Xiaojun Lian
Kunil K Raval
Matthew R Barron
Luqia Hou
Andrew G Soerens
Junying Yu
Sean P Palecek
Gary E Lyons
James A Thomson
Todd J Herron
José Jalife
Timothy J Kamp
University of Michigan–Ann Arbor · USWiCell · USCellular Dynamics International (United States) · USUniversity of California, Santa Barbara · USUniversity of Wisconsin–Madison · US

Funding

THREE DIMENSIONAL VORTEX LIKE REENTRY IN CORONARY PERFUSED VENTRICULAR WALLP01HL039707 · NHLBI · UPSTATE MEDICAL UNIVERSITY · PI JALIFE, JOSE S · 1990 to 2010
$19.0M
P3: Biophysical Mechanisms in two Arhythmogenic DiseasesP01HL087226 · NHLBI · UPSTATE MEDICAL UNIVERSITY · PI JALIFE, JOSE S · 2007 to 2012
$10.3M
INTEGRATED TRAINING FOR PHYSICIAN-SCIENTISTST32GM008692 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI BURKARD, MARK E · 1998 to 2020
$10.3M
Midwest Progenitor Cell ConsortiumU01HL099773 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI THOMSON, JAMES ALEXANDER · 2009 to 2015
$7.8M
Regulating human pluripotent stem cell differentiation by colony confinementR01EB007534 · NIBIB · UNIVERSITY OF WISCONSIN-MADISON · PI PALECEK, SEAN P · 2007 to 2019
$4.1M
Embryonic Stem Cell-based Therapies for Myocardial InfarctionR01HL084615 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI KAMP, TIMOTHY J. · 2007 to 2010
$1.6M
NHLBI NIH HHS P01 HL039707NHLBI NIH HHS P01-HL039707NHLBI NIH HHS P01 HL087226NHLBI NIH HHS P01-HL087226NHLBI NIH HHS R01 HL08416NHLBI NIH HHS R01 HL084615NHLBI NIH HHS U01 HL099773NIBIB NIH HHS R01 EB007534NIGMS NIH HHS T32 GM008692
6 · The paper itself

Abstract

rationaleCardiomyocytes (CMs) differentiated from human pluripotent stem cells (PSCs) are increasingly being used for cardiovascular research, including disease modeling, and hold promise for clinical applications. Current cardiac differentiation protocols exhibit variable success across different PSC lines and are primarily based on the application of growth factors. However, extracellular matrix is also fundamentally involved in cardiac development from the earliest morphogenetic events, such as gastrulation.

objectiveWe sought to develop a more effective protocol for cardiac differentiation of human PSCs by using extracellular matrix in combination with growth factors known to promote cardiogenesis. METHODS AND

resultsPSCs were cultured as monolayers on Matrigel, an extracellular matrix preparation, and subsequently overlayed with Matrigel. The matrix sandwich promoted an epithelial-to-mesenchymal transition as in gastrulation with the generation of N-cadherin-positive mesenchymal cells. Combining the matrix sandwich with sequential application of growth factors (Activin A, bone morphogenetic protein 4, and basic fibroblast growth factor) generated CMs with high purity (up to 98%) and yield (up to 11 CMs/input PSC) from multiple PSC lines. The resulting CMs progressively matured over 30 days in culture based on myofilament expression pattern and mitotic activity. Action potentials typical of embryonic nodal, atrial, and ventricular CMs were observed, and monolayers of electrically coupled CMs modeled cardiac tissue and basic arrhythmia mechanisms.

conclusionsDynamic extracellular matrix application promoted epithelial-mesenchymal transition of human PSCs and complemented growth factor signaling to enable robust cardiac differentiation.

Indexed as

CollagenLamininProteoglycansActivinsBone Morphogenetic Protein 4Cell Culture TechniquesCell DifferentiationCell LineCells, CulturedDrug CombinationsEpithelial-Mesenchymal TransitionExtracellular MatrixFibroblast Growth Factor 2HumansIntercellular Signaling Peptides and ProteinsMyocytes, Cardiacactivin AActivinsBMP4 protein, humanBone Morphogenetic Protein 4CollagenDrug CombinationsFibroblast Growth Factor 2Intercellular Signaling Peptides and ProteinsLamininmatrigelProteoglycans

Identifiers

PMID22912385
PMCPMC3482164
OpenAlexW2158128644

What OpenQuestion holds

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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.