Evidence map›Paper›PMID 24735830›Full record

ArticleJournal of molecular and cellular cardiology2014

Tri-iodo-l-thyronine promotes the maturation of human cardiomyocytes-derived from induced pluripotent stem cells.

Xiulan Yang, Marita Rodriguez, Lil Pabon, Karin A Fischer, Hans Reinecke, Michael Regnier, Nathan J Sniadecki, Hannele Ruohola-Baker, Charles E Murry

Abstract read
In one paragraph

Article in Journal of molecular and cellular cardiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 271 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
271citing papers in PubMed, 2 pooled it
14.0field-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

271 citing papers in PubMed, 2 syntheses or guidelines pooled it, 425 citations in OpenAlex.

  1. Engineering the maturation of stem cell-derived cardiomyocytes.Frontiers in bioengineering and biotechnology · 2023
    Pooled it
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  3. Review
  4. Immature and mature myocardium in the pathophysiology of hypertrophic cardiomyopathy.Journal of molecular and cellular cardiology plus · 2026
    Review
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211 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

9 authors at 1 institution in 1 country.

Xiulan YangDepartment of Pathology, University of Washington, Seattle, WA 98109, USA; Center for Cardiovascular Biology, University of Washington, Seattle, WA 98109, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98109, USA.
Marita RodriguezDepartment of Mechanical Engineering, University of Washington, Seattle, WA 98109, USA.
Lil PabonDepartment of Pathology, University of Washington, Seattle, WA 98109, USA; Center for Cardiovascular Biology, University of Washington, Seattle, WA 98109, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98109, USA.
Karin A FischerDepartment of Biochemistry, University of Washington, Seattle, WA 98109, USA.
Hans ReineckeDepartment of Pathology, University of Washington, Seattle, WA 98109, USA; Center for Cardiovascular Biology, University of Washington, Seattle, WA 98109, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98109, USA.
Michael RegnierDepartment of Bioengineering, University of Washington, Seattle, WA 98109, USA; Center for Cardiovascular Biology, University of Washington, Seattle, WA 98109, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98109, USA.
Nathan J SniadeckiDepartment of Mechanical Engineering, University of Washington, Seattle, WA 98109, USA; Department of Bioengineering, University of Washington, Seattle, WA 98109, USA.
Hannele Ruohola-BakerDepartment of Biochemistry, University of Washington, Seattle, WA 98109, USA.
Charles E MurryDepartment of Pathology, University of Washington, Seattle, WA 98109, USA; Department of Bioengineering, University of Washington, Seattle, WA 98109, USA; Department of Medicine/Cardiology, University of Washington, Seattle, WA 98109, USA; Center for Cardiovascular Biology, University of Washington, Seattle, WA 98109, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98109, USA. Electronic address: murry@uw.edu.
University of Washington · US

Funding

Self Renewal and Differentiation of Human Embryonic Stem CellsP01GM081619 · NIGMS · UNIVERSITY OF WASHINGTON · PI REH, THOMAS A · 2007 to 2017
$20.6M
Vascularization and Growth of Human Myocardial GraftsP01HL094374 · NHLBI · UNIVERSITY OF WASHINGTON · PI MINAMI, ELINA · 2010 to 2014
$14.5M
Expansion of cardiac and hematopoietic progenitors by Wnt and NotchU01HL100405 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI EPSTEIN, JONATHAN A., MORRISEY, EDWARD E · 2009 to 2015
$8.1M
Cell-Based Cardiac RepairR01HL084642 · NHLBI · UNIVERSITY OF WASHINGTON · PI MURRY, CHARLES E · 2007 to 2014
$4.9M
Bioengineering Cardiovascular Training GrantT32EB001650 · NIBIB · UNIVERSITY OF WASHINGTON · PI REGNIER, MICHAEL · 2004 to 2019
$3.6M
EFFECT OF R1R2 OVER-EXPRESSION ON CARDIAC FUNCTIONR01HL111197 · NHLBI · UNIVERSITY OF WASHINGTON · PI REGNIER, MICHAEL · 2012 to 2015
$2.3M
Acquisition of Embryonic Stem Cell Metabolic Signature - Minority SupplementR01GM097372 · NIGMS · UNIVERSITY OF WASHINGTON · PI RUOHOLA-BAKER, HANNELE · 2011 to 2014
$1.3M
NHLBI NIH HHS P01 HL094374NHLBI NIH HHS P01HL094374NHLBI NIH HHS R01 HL084642NHLBI NIH HHS R01HL084642NHLBI NIH HHS R01 HL111197NHLBI NIH HHS U01 HL100405NHLBI NIH HHS U01HL100405NIBIB NIH HHS T32 EB001650NIGMS NIH HHS P01 GM081619NIGMS NIH HHS P01GM081619NIGMS NIH HHS R01 GM097372
6 · The paper itself

Abstract

backgroundCardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) have great potential as a cell source for therapeutic applications such as regenerative medicine, disease modeling, drug screening, and toxicity testing. This potential is limited, however, by the immature state of the cardiomyocytes acquired using current protocols. Tri-iodo-l-thyronine (T3) is a growth hormone that is essential for optimal heart growth. In this study, we investigated the effect of T3 on hiPSC-CM maturation. METHODS AND

resultsA one-week treatment with T3 increased cardiomyocyte size, anisotropy, and sarcomere length. T3 treatment was associated with reduced cell cycle activity, manifest as reduced DNA synthesis and increased expression of the cyclin-dependent kinase inhibitor p21. Contractile force analyses were performed on individual cardiomyocytes using arrays of microposts, revealing an almost two-fold higher force per-beat after T3 treatment and also an enhancement in contractile kinetics. This improvement in force generation was accompanied by an increase in rates of calcium release and reuptake, along with a significant increase in sarcoendoplasmic reticulum ATPase expression. Finally, although mitochondrial genomes were not numerically increased, extracellular flux analysis showed a significant increase in maximal mitochondrial respiratory capacity and respiratory reserve capability after T3 treatment.

conclusionsUsing a broad spectrum of morphological, molecular, and functional parameters, we conclude that T3 is a driver for hiPSC-CM maturation. T3 treatment may enhance the utility of hiPSC-CMs for therapy, disease modeling, or drug/toxicity screens.

Indexed as

AnimalsCalciumCell CycleCell DifferentiationCells, CulturedCulture Media, ConditionedCyclin-Dependent Kinase Inhibitor p21FibroblastsGene ExpressionHumansInduced Pluripotent Stem CellsLungMiceMitochondriaMyocytes, CardiacOxidative PhosphorylationCalciumCulture Media, ConditionedCyclin-Dependent Kinase Inhibitor p21Sarcoplasmic Reticulum Calcium-Transporting ATPasesTriiodothyronineCardiomyocyte maturationContractile forceHuman induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs)MitochondriaTri-iodo-l-thyronine

Identifiers

PMID24735830
PMCPMC4041732
OpenAlexW2042091538

What OpenQuestion holds

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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.