Evidence map›Paper›PMID 27069088›Full record

ArticleCirculation. Arrhythmia and electrophysiology2016

Extracellular Matrix-Mediated Maturation of Human Pluripotent Stem Cell-Derived Cardiac Monolayer Structure and Electrophysiological Function.

Todd J Herron, Andre Monteiro Da Rocha, Katherine F Campbell, Daniela Ponce-Balbuena, B Cicero Willis, Guadalupe Guerrero-Serna, Qinghua Liu, Matt Klos, Hassan Musa, Manuel Zarzoso and 5 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation. Arrhythmia and electrophysiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 168 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
168citing papers in PubMed, 2 pooled it
22.0field-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

168 citing papers in PubMed, 2 syntheses or guidelines pooled it, 259 citations in OpenAlex.

  1. Engineering the maturation of stem cell-derived cardiomyocytes.Frontiers in bioengineering and biotechnology · 2023
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108 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

15 authors at 3 institutions in 2 countries.

Todd J HerronFrom the Center for Arrhythmia Research, Department of Internal Medicine, Cardiovascular Research Center, University of Michigan, Ann Arbor, MI (T.J.H., A.M.D.R., K.C., D.P.-B., B.C.W., G.G.-S., Q.L., J.F., J.A., S.M., J.J.); Department of Medicine, University of California San Diego, La Jolla, CA (M.K.); Davis Heart and Lung Research Institute, Ohio State University, Columbus, OH (H.M.); Shanxi Medical University, Zhejiang, China (Q.L.); and University of Valencia, Valencia, Spain (M.Z., A.B.). toddherr@umich.edu.
Andre Monteiro Da RochaFrom the Center for Arrhythmia Research, Department of Internal Medicine, Cardiovascular Research Center, University of Michigan, Ann Arbor, MI (T.J.H., A.M.D.R., K.C., D.P.-B., B.C.W., G.G.-S., Q.L., J.F., J.A., S.M., J.J.); Department of Medicine, University of California San Diego, La Jolla, CA (M.K.); Davis Heart and Lung Research Institute, Ohio State University, Columbus, OH (H.M.); Shanxi Medical University, Zhejiang, China (Q.L.); and University of Valencia, Valencia, Spain (M.Z., A.B.).
Katherine F CampbellFrom the Center for Arrhythmia Research, Department of Internal Medicine, Cardiovascular Research Center, University of Michigan, Ann Arbor, MI (T.J.H., A.M.D.R., K.C., D.P.-B., B.C.W., G.G.-S., Q.L., J.F., J.A., S.M., J.J.); Department of Medicine, University of California San Diego, La Jolla, CA (M.K.); Davis Heart and Lung Research Institute, Ohio State University, Columbus, OH (H.M.); Shanxi Medical University, Zhejiang, China (Q.L.); and University of Valencia, Valencia, Spain (M.Z., A.B.).
Daniela Ponce-BalbuenaFrom the Center for Arrhythmia Research, Department of Internal Medicine, Cardiovascular Research Center, University of Michigan, Ann Arbor, MI (T.J.H., A.M.D.R., K.C., D.P.-B., B.C.W., G.G.-S., Q.L., J.F., J.A., S.M., J.J.); Department of Medicine, University of California San Diego, La Jolla, CA (M.K.); Davis Heart and Lung Research Institute, Ohio State University, Columbus, OH (H.M.); Shanxi Medical University, Zhejiang, China (Q.L.); and University of Valencia, Valencia, Spain (M.Z., A.B.).
B Cicero WillisFrom the Center for Arrhythmia Research, Department of Internal Medicine, Cardiovascular Research Center, University of Michigan, Ann Arbor, MI (T.J.H., A.M.D.R., K.C., D.P.-B., B.C.W., G.G.-S., Q.L., J.F., J.A., S.M., J.J.); Department of Medicine, University of California San Diego, La Jolla, CA (M.K.); Davis Heart and Lung Research Institute, Ohio State University, Columbus, OH (H.M.); Shanxi Medical University, Zhejiang, China (Q.L.); and University of Valencia, Valencia, Spain (M.Z., A.B.).
Guadalupe Guerrero-SernaFrom the Center for Arrhythmia Research, Department of Internal Medicine, Cardiovascular Research Center, University of Michigan, Ann Arbor, MI (T.J.H., A.M.D.R., K.C., D.P.-B., B.C.W., G.G.-S., Q.L., J.F., J.A., S.M., J.J.); Department of Medicine, University of California San Diego, La Jolla, CA (M.K.); Davis Heart and Lung Research Institute, Ohio State University, Columbus, OH (H.M.); Shanxi Medical University, Zhejiang, China (Q.L.); and University of Valencia, Valencia, Spain (M.Z., A.B.).
Qinghua LiuFrom the Center for Arrhythmia Research, Department of Internal Medicine, Cardiovascular Research Center, University of Michigan, Ann Arbor, MI (T.J.H., A.M.D.R., K.C., D.P.-B., B.C.W., G.G.-S., Q.L., J.F., J.A., S.M., J.J.); Department of Medicine, University of California San Diego, La Jolla, CA (M.K.); Davis Heart and Lung Research Institute, Ohio State University, Columbus, OH (H.M.); Shanxi Medical University, Zhejiang, China (Q.L.); and University of Valencia, Valencia, Spain (M.Z., A.B.).
Matt KlosFrom the Center for Arrhythmia Research, Department of Internal Medicine, Cardiovascular Research Center, University of Michigan, Ann Arbor, MI (T.J.H., A.M.D.R., K.C., D.P.-B., B.C.W., G.G.-S., Q.L., J.F., J.A., S.M., J.J.); Department of Medicine, University of California San Diego, La Jolla, CA (M.K.); Davis Heart and Lung Research Institute, Ohio State University, Columbus, OH (H.M.); Shanxi Medical University, Zhejiang, China (Q.L.); and University of Valencia, Valencia, Spain (M.Z., A.B.).
Hassan MusaFrom the Center for Arrhythmia Research, Department of Internal Medicine, Cardiovascular Research Center, University of Michigan, Ann Arbor, MI (T.J.H., A.M.D.R., K.C., D.P.-B., B.C.W., G.G.-S., Q.L., J.F., J.A., S.M., J.J.); Department of Medicine, University of California San Diego, La Jolla, CA (M.K.); Davis Heart and Lung Research Institute, Ohio State University, Columbus, OH (H.M.); Shanxi Medical University, Zhejiang, China (Q.L.); and University of Valencia, Valencia, Spain (M.Z., A.B.).
Manuel ZarzosoFrom the Center for Arrhythmia Research, Department of Internal Medicine, Cardiovascular Research Center, University of Michigan, Ann Arbor, MI (T.J.H., A.M.D.R., K.C., D.P.-B., B.C.W., G.G.-S., Q.L., J.F., J.A., S.M., J.J.); Department of Medicine, University of California San Diego, La Jolla, CA (M.K.); Davis Heart and Lung Research Institute, Ohio State University, Columbus, OH (H.M.); Shanxi Medical University, Zhejiang, China (Q.L.); and University of Valencia, Valencia, Spain (M.Z., A.B.).
Alexandra BizyFrom the Center for Arrhythmia Research, Department of Internal Medicine, Cardiovascular Research Center, University of Michigan, Ann Arbor, MI (T.J.H., A.M.D.R., K.C., D.P.-B., B.C.W., G.G.-S., Q.L., J.F., J.A., S.M., J.J.); Department of Medicine, University of California San Diego, La Jolla, CA (M.K.); Davis Heart and Lung Research Institute, Ohio State University, Columbus, OH (H.M.); Shanxi Medical University, Zhejiang, China (Q.L.); and University of Valencia, Valencia, Spain (M.Z., A.B.).
Jamie FurnessFrom the Center for Arrhythmia Research, Department of Internal Medicine, Cardiovascular Research Center, University of Michigan, Ann Arbor, MI (T.J.H., A.M.D.R., K.C., D.P.-B., B.C.W., G.G.-S., Q.L., J.F., J.A., S.M., J.J.); Department of Medicine, University of California San Diego, La Jolla, CA (M.K.); Davis Heart and Lung Research Institute, Ohio State University, Columbus, OH (H.M.); Shanxi Medical University, Zhejiang, China (Q.L.); and University of Valencia, Valencia, Spain (M.Z., A.B.).
Justus AnumonwoFrom the Center for Arrhythmia Research, Department of Internal Medicine, Cardiovascular Research Center, University of Michigan, Ann Arbor, MI (T.J.H., A.M.D.R., K.C., D.P.-B., B.C.W., G.G.-S., Q.L., J.F., J.A., S.M., J.J.); Department of Medicine, University of California San Diego, La Jolla, CA (M.K.); Davis Heart and Lung Research Institute, Ohio State University, Columbus, OH (H.M.); Shanxi Medical University, Zhejiang, China (Q.L.); and University of Valencia, Valencia, Spain (M.Z., A.B.).
Sergey MironovFrom the Center for Arrhythmia Research, Department of Internal Medicine, Cardiovascular Research Center, University of Michigan, Ann Arbor, MI (T.J.H., A.M.D.R., K.C., D.P.-B., B.C.W., G.G.-S., Q.L., J.F., J.A., S.M., J.J.); Department of Medicine, University of California San Diego, La Jolla, CA (M.K.); Davis Heart and Lung Research Institute, Ohio State University, Columbus, OH (H.M.); Shanxi Medical University, Zhejiang, China (Q.L.); and University of Valencia, Valencia, Spain (M.Z., A.B.).
José JalifeFrom the Center for Arrhythmia Research, Department of Internal Medicine, Cardiovascular Research Center, University of Michigan, Ann Arbor, MI (T.J.H., A.M.D.R., K.C., D.P.-B., B.C.W., G.G.-S., Q.L., J.F., J.A., S.M., J.J.); Department of Medicine, University of California San Diego, La Jolla, CA (M.K.); Davis Heart and Lung Research Institute, Ohio State University, Columbus, OH (H.M.); Shanxi Medical University, Zhejiang, China (Q.L.); and University of Valencia, Valencia, Spain (M.Z., A.B.).
Shanxi Medical University · CNLung Institute · USUniversity of California, San Diego · US

Funding

THREE DIMENSIONAL VORTEX LIKE REENTRY IN CORONARY PERFUSED VENTRICULAR WALLP01HL039707 · NHLBI · UPSTATE MEDICAL UNIVERSITY · PI ZAITSEV, ALEXEY V · 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
Intermolecular Interactions of NaV1.5 and Kir2.1 In Ion Channel DiseasesR01HL122352 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BERENFELD, OMER · 2015 to 2018
$1.9M
Arrhythmogenicity of human SAP97 Mutations in patient specific iPSC-CMs and MiceR01HL124319 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ANUMONWO, JUSTUS M · 2015 to 2017
$1.3M
NHLBI NIH HHS P01 HL039707NHLBI NIH HHS P01-HL039707NHLBI NIH HHS P01 HL087226NHLBI NIH HHS P01-HL087226NHLBI NIH HHS R01 HL122352NHLBI NIH HHS R01 HL124319
6 · The paper itself

Abstract

backgroundHuman pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) monolayers generated to date display an immature embryonic-like functional and structural phenotype that limits their utility for research and cardiac regeneration. In particular, the electrophysiological function of hPSC-CM monolayers and bioengineered constructs used to date are characterized by slow electric impulse propagation velocity and immature action potential profiles. METHODS AND

resultsHere, we have identified an optimal extracellular matrix for significant electrophysiological and structural maturation of hPSC-CM monolayers. hPSC-CM plated in the optimal extracellular matrix combination have impulse propagation velocities ≈2× faster than previously reported (43.6±7.0 cm/s; n=9) and have mature cardiomyocyte action potential profiles, including hyperpolarized diastolic potential and rapid action potential upstroke velocity (146.5±17.7 V/s; n=5 monolayers). In addition, the optimal extracellular matrix promoted hypertrophic growth of cardiomyocytes and the expression of key mature sarcolemmal (SCN5A, Kir2.1, and connexin43) and myofilament markers (cardiac troponin I). The maturation process reported here relies on activation of integrin signaling pathways: neutralization of β1 integrin receptors via blocking antibodies and pharmacological blockade of focal adhesion kinase activation prevented structural maturation.

conclusionsMaturation of human stem cell-derived cardiomyocyte monolayers is achieved in a 1-week period by plating cardiomyocytes on PDMS (polydimethylsiloxane) coverslips rather than on conventional 2-dimensional cell culture formats, such as glass coverslips or plastic dishes. Activation of integrin signaling and focal adhesion kinase is essential for significant maturation of human cardiac monolayers.

Indexed as

Action PotentialsCell DifferentiationCell LineElectrophysiological PhenomenaExtracellular MatrixHumansInduced Pluripotent Stem CellsMyocytes, CardiacSignal Transductioncardiac electrophysiologycell culture techniqueshardnessinduced pluripotent stem cellsintegrin alpha5beta1myocytes, cardiactroponin I

Identifiers

PMID27069088
PMCPMC4833010
OpenAlexW2337274534

What OpenQuestion holds

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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.