Evidence map›Paper›PMID 35478228›Full record

ArticleNature biomedical engineering2022

Metabolically driven maturation of human-induced-pluripotent-stem-cell-derived cardiac microtissues on microfluidic chips.

Nathaniel Huebsch, Berenice Charrez, Gabriel Neiman, Brian Siemons, Steven C Boggess, Samuel Wall, Verena Charwat, Karoline H Jæger, David Cleres, Åshild Telle and 10 more

Open access · greenAbstract read
In one paragraph

Article in Nature biomedical engineering, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
79citing papers in PubMed, 2 pooled it
7.8field-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

79 citing papers in PubMed, 2 syntheses or guidelines pooled it, 104 citations in OpenAlex.

  1. Engineering the maturation of stem cell-derived cardiomyocytes.Frontiers in bioengineering and biotechnology · 2023
    Pooled it
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  15. Sometimes extracellular recordings fail for good reasons.NPJ systems biology and applications · 2026
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19 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

20 authors at 5 institutions in 2 countries.

Nathaniel Huebsch *Department of Bioengineering and California Institute for Quantitative Biosciences (QB3), University of California at Berkeley, Berkeley, CA, USA.ORCID http://orcid.org/0000-0002-3329-0214
Berenice Charrez *Department of Bioengineering and California Institute for Quantitative Biosciences (QB3), University of California at Berkeley, Berkeley, CA, USA.
Gabriel NeimanDepartment of Bioengineering and California Institute for Quantitative Biosciences (QB3), University of California at Berkeley, Berkeley, CA, USA.
Brian SiemonsDepartment of Bioengineering and California Institute for Quantitative Biosciences (QB3), University of California at Berkeley, Berkeley, CA, USA.
Steven C BoggessDepartment of Chemistry, University of California at Berkeley, Berkeley, CA, USA.ORCID http://orcid.org/0000-0001-9232-4122
Samuel WallSimula Research Laboratory, Oslo, Norway.
Verena CharwatDepartment of Bioengineering and California Institute for Quantitative Biosciences (QB3), University of California at Berkeley, Berkeley, CA, USA.ORCID http://orcid.org/0000-0002-2222-3702
Karoline H JægerSimula Research Laboratory, Oslo, Norway.ORCID http://orcid.org/0000-0003-4234-9094
David CleresDepartment of Bioengineering and California Institute for Quantitative Biosciences (QB3), University of California at Berkeley, Berkeley, CA, USA.
Åshild TelleSimula Research Laboratory, Oslo, Norway.ORCID http://orcid.org/0000-0001-5399-4094
Felipe T Lee-MontielDepartment of Bioengineering and California Institute for Quantitative Biosciences (QB3), University of California at Berkeley, Berkeley, CA, USA.ORCID http://orcid.org/0000-0002-8326-6036
Nicholas C JeffreysDepartment of Bioengineering and California Institute for Quantitative Biosciences (QB3), University of California at Berkeley, Berkeley, CA, USA.
Nikhil DeveshwarDepartment of Bioengineering and California Institute for Quantitative Biosciences (QB3), University of California at Berkeley, Berkeley, CA, USA.
Andrew G EdwardsDepartment of Pharmacology, School of Medicine, University of California, Davis, CA, USA.
Jonathan SerranoDepartment of Pathology, New York University Langone Health and Medical School, New York, NY, USA.
Matija SnuderlDepartment of Pathology, New York University Langone Health and Medical School, New York, NY, USA.
Andreas StahlDepartment of Nutritional Sciences and Toxicology, University of California at Berkeley, Berkeley, CA, USA.
Aslak TveitoSimula Research Laboratory, Oslo, Norway.ORCID http://orcid.org/0000-0003-2362-146X
Evan W MillerDepartment of Chemistry, University of California at Berkeley, Berkeley, CA, USA.ORCID http://orcid.org/0000-0002-6556-7679
Kevin E HealyDepartment of Bioengineering and California Institute for Quantitative Biosciences (QB3), University of California at Berkeley, Berkeley, CA, USA. kehealy@berkeley.edu.ORCID http://orcid.org/0000-0002-8524-3671
QB3 · USSimula Research Laboratory · NOUniversity of California, Berkeley · USNYU Langone Health · USUniversity of California, Davis · US

Funding

Univ of Calif Berkeley Chemistry-Biology Interface ProgramT32GM066698 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI CHANG, CHRISTOPHER J., FRANCIS, MATTHEW B · 2004 to 2023
$7.5M
Human heart-on-a-chip for screening cardiomyopathy and chemotherapeutic cardiotoxicityR01HL130417 · NHLBI · UNIVERSITY OF CALIFORNIA BERKELEY · PI HEALY, KEVIN EDWARD · 2017 to 2020
$2.3M
New Chemical Tools for Exploring Cellular PhysiologyR35GM119855 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI MILLER, EVAN WALKER · 2016 to 2020
$1.3M
NHLBI NIH HHS R01 HL130417NIGMS NIH HHS R35 GM119855NIGMS NIH HHS T32 GM066698
6 · The paper itself

Abstract

The immature physiology of cardiomyocytes derived from human induced pluripotent stem cells (hiPSCs) limits their utility for drug screening and disease modelling. Here we show that suitable combinations of mechanical stimuli and metabolic cues can enhance the maturation of hiPSC-derived cardiomyocytes, and that the maturation-inducing cues have phenotype-dependent effects on the cells' action-potential morphology and calcium handling. By using microfluidic chips that enhanced the alignment and extracellular-matrix production of cardiac microtissues derived from genetically distinct sources of hiPSC-derived cardiomyocytes, we identified fatty-acid-enriched maturation media that improved the cells' mitochondrial structure and calcium handling, and observed divergent cell-source-dependent effects on action-potential duration (APD). Specifically, in the presence of maturation media, tissues with abnormally prolonged APDs exhibited shorter APDs, and tissues with aberrantly short APDs displayed prolonged APDs. Regardless of cell source, tissue maturation reduced variabilities in spontaneous beat rate and in APD, and led to converging cell phenotypes (with APDs within the 300-450 ms range characteristic of human left ventricular cardiomyocytes) that improved the modelling of the effects of pro-arrhythmic drugs on cardiac tissue.

Indexed as

Induced Pluripotent Stem CellsCalciumCell DifferentiationHumansMicrofluidicsMyocytes, CardiacCalcium

Identifiers

PMID35478228
PMCPMC10344596
OpenAlexW4225089642

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.