Evidence map›Paper›PMID 27095412›Full record

ArticleScientific reports2016

Miniaturized iPS-Cell-Derived Cardiac Muscles for Physiologically Relevant Drug Response Analyses.

Nathaniel Huebsch, Peter Loskill, Nikhil Deveshwar, C Ian Spencer, Luke M Judge, Mohammad A Mandegar, Cade B Fox, Tamer M A Mohamed, Zhen Ma, Anurag Mathur and 9 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 135 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
135citing papers in PubMed, 1 pooled it
30.4field-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

135 citing papers in PubMed, 1 synthesis or guideline pooled it, 229 citations in OpenAlex.

  1. Pooled it
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  16. Generation and applications of cardiac spheroids.npj biomedical innovations · 2025
    Review
  17. Advances in human induced pluripotent stem cell (hiPSC)-based disease modelling in cardiogenetics.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2025
    Article
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75 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

19 authors at 4 institutions in 2 countries.

Nathaniel HuebschGladstone Institute of Cardiovascular Disease, San Francisco, CA 94158.
Peter LoskillDepartment of Bioengineering and California Institute for Quantitative Biosciences (QB3), University of California at Berkeley, Berkeley, California 94720, USA.
Nikhil DeveshwarDepartment of Bioengineering and California Institute for Quantitative Biosciences (QB3), University of California at Berkeley, Berkeley, California 94720, USA.
C Ian SpencerGladstone Institute of Cardiovascular Disease, San Francisco, CA 94158.
Luke M JudgeGladstone Institute of Cardiovascular Disease, San Francisco, CA 94158.
Mohammad A MandegarGladstone Institute of Cardiovascular Disease, San Francisco, CA 94158.
Cade B FoxUniversity of California, San Francisco, Schools of Pharmacy and Medicine, Department of Bioengineering and Therapeutic Sciences, San Francisco, CA 94158.
Tamer M A MohamedGladstone Institute of Cardiovascular Disease, San Francisco, CA 94158.
Zhen MaDepartment of Bioengineering and California Institute for Quantitative Biosciences (QB3), University of California at Berkeley, Berkeley, California 94720, USA.
Anurag MathurDepartment of Bioengineering and California Institute for Quantitative Biosciences (QB3), University of California at Berkeley, Berkeley, California 94720, USA.
Alice M SheehanGladstone Institute of Cardiovascular Disease, San Francisco, CA 94158.
Annie TruongGladstone Institute of Cardiovascular Disease, San Francisco, CA 94158.
Mike SaxtonGladstone Institute of Cardiovascular Disease, San Francisco, CA 94158.
Jennie YooGladstone Institute of Cardiovascular Disease, San Francisco, CA 94158.
Deepak SrivastavaGladstone Institute of Cardiovascular Disease, San Francisco, CA 94158.
Tejal A DesaiUniversity of California, San Francisco, Schools of Pharmacy and Medicine, Department of Bioengineering and Therapeutic Sciences, San Francisco, CA 94158.
Po-Lin SoGladstone Institute of Cardiovascular Disease, San Francisco, CA 94158.
Kevin E HealyDepartment of Bioengineering and California Institute for Quantitative Biosciences (QB3), University of California at Berkeley, Berkeley, California 94720, USA.
Bruce R ConklinGladstone Institute of Cardiovascular Disease, San Francisco, CA 94158.
Gladstone Institutes · USUniversity of California, San Francisco · USQB3 · USUniversity of California, Berkeley · US

Funding

Engaging University of California Stakeholders for Biorespository ResearchUL1TR000004 · NCATS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GRANDIS, JENNIFER RUBIN · 2012 to 2015
$78.0M
Transcriptional Networks During Cardiac DifferentiationP01HL089707 · NHLBI · J. DAVID GLADSTONE INSTITUTES · PI SRIVASTAVA, DEEPAK · 2008 to 2017
$20.4M
The Epigenetic Landscape of Heart DevelopmentU01HL098179 · NHLBI · J. DAVID GLADSTONE INSTITUTES · PI BOYER, LAURIE A, BRUNEAU, BENOIT GAETAN · 2009 to 2014
$10.0M
Induced Pluripotent Stem Cells in the Understanding and Treatment of Heart DiseasU01HL100406 · NHLBI · J. DAVID GLADSTONE INSTITUTES · PI BRUNEAU, BENOIT GAETAN, CONKLIN, BRUCE R · 2009 to 2015
$9.4M
Training in Developmental Cardiovascular BiologyT32HL007544 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SRIVASTAVA, DEEPAK · 1985 to 2021
$4.5M
Modeling metabolic interactions of liver and fat with integrated microphysiological systemsUH3TR000487 · NCATS · UNIVERSITY OF CALIFORNIA BERKELEY · PI HEALY, KEVIN EDWARD · 2014 to 2016
$2.9M
Disease Specific Cardiac Tissue ModelsR01HL108677 · NHLBI · UNIVERSITY OF CALIFORNIA BERKELEY · PI CONKLIN, BRUCE R, HEALY, KEVIN EDWARD · 2011 to 2014
$2.4M
Child Health Career Development Program at UCSFK12HD072222 · NICHD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FERRIERO, DONNA M. · 2013 to 2017
$2.0M
Identifying Therapeutic Targets for RNA Splicing-Related CardiomyopathyR01HL130533 · NHLBI · J. DAVID GLADSTONE INSTITUTES · PI CONKLIN, BRUCE R · 2016 to 2019
$1.8M
Disease-Specific Integrated Microphysiological Human Tissue ModelsUH2TR000487 · NCATS · UNIVERSITY OF CALIFORNIA BERKELEY · PI HEALY, KEVIN EDWARD, LEE, LUKE P. · 2012 to 2013
$1.8M
Enabling Technologies for hES Cell Self-RenewalR01HL096525 · NHLBI · UNIVERSITY OF CALIFORNIA BERKELEY · PI HEALY, KEVIN EDWARD · 2009 to 2013
$1.8M
PHARMACOLOGY AND PHYSIOLOGY IN BIOMEDICAL RESEARCHF31GM009614 · NIGMS · UNIVERSITY OF CALIFORNIA SAN DIEGO · PI MUNGER, KAREN · 1985 to 1988
–
CIHR 129844NCATS NIH HHS UH2 TR000487NCATS NIH HHS UH2TR000487NCATS NIH HHS UH3 TR000487NCATS NIH HHS UL1 TR000004NHLBI NIH HHS P01 HL089707NHLBI NIH HHS P01HL089707NHLBI NIH HHS R01 HL096525NHLBI NIH HHS R01HL096525NHLBI NIH HHS R01 HL108677NHLBI NIH HHS R01HL108677NHLBI NIH HHS R01 HL130533NHLBI NIH HHS T32 HL007544NHLBI NIH HHS U01 HL098179NHLBI NIH HHS U01HL098179NHLBI NIH HHS U01 HL100406NHLBI NIH HHS U01HL100406NICHD NIH HHS K12 HD072222NIGMS NIH HHS U01GM09614
6 · The paper itself

Abstract

Tissue engineering approaches have the potential to increase the physiologic relevance of human iPS-derived cells, such as cardiomyocytes (iPS-CM). However, forming Engineered Heart Muscle (EHM) typically requires >1 million cells per tissue. Existing miniaturization strategies involve complex approaches not amenable to mass production, limiting the ability to use EHM for iPS-based disease modeling and drug screening. Micro-scale cardiospheres are easily produced, but do not facilitate assembly of elongated muscle or direct force measurements. Here we describe an approach that combines features of EHM and cardiospheres: Micro-Heart Muscle (μHM) arrays, in which elongated muscle fibers are formed in an easily fabricated template, with as few as 2,000 iPS-CM per individual tissue. Within μHM, iPS-CM exhibit uniaxial contractility and alignment, robust sarcomere assembly, and reduced variability and hypersensitivity in drug responsiveness, compared to monolayers with the same cellular composition. μHM mounted onto standard force measurement apparatus exhibited a robust Frank-Starling response to external stretch, and a dose-dependent inotropic response to the β-adrenergic agonist isoproterenol. Based on the ease of fabrication, the potential for mass production and the small number of cells required to form μHM, this system provides a potentially powerful tool to study cardiomyocyte maturation, disease and cardiotoxicology in vitro.

Indexed as

Cell DifferentiationCells, CulturedFluorescent Antibody TechniqueHumansInduced Pluripotent Stem CellsMyocytes, CardiacSarcomeresStromal Cells

Identifiers

PMID27095412
PMCPMC4837370
OpenAlexW2338837420

What OpenQuestion holds

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Read underepoch 390

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.