Evidence map›Paper›PMID 31564645›Full record

ArticleStem cell reports2019

Fatty Acids Enhance the Maturation of Cardiomyocytes Derived from Human Pluripotent Stem Cells.

Xiulan Yang, Marita L Rodriguez, Andrea Leonard, Lihua Sun, Karin A Fischer, Yuliang Wang, Julia Ritterhoff, Limei Zhao, Stephen C Kolwicz, Lil Pabon and 6 more

Open access · goldAbstract read
In one paragraph

Article in Stem cell reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 197 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
197citing papers in PubMed, 3 pooled it
12.1field-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

197 citing papers in PubMed, 3 syntheses or guidelines pooled it, 305 citations in OpenAlex.

  1. Engineering the maturation of stem cell-derived cardiomyocytes.Frontiers in bioengineering and biotechnology · 2023
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  18. Cytochrome P450-derived metabolites of docosahexaenoic acid or arachidonic acid enhance contractility of cultured rat cardiomyocytes: a pilot study.Journal of artificial organs : the official journal of the Japanese Society for Artificial Organs · 2026
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137 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 2 institutions in 2 countries.

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, 850 Republican Street, Brotman Building Room 453, Seattle, WA 98109, USA.
Marita L RodriguezDepartment of Mechanical Engineering, 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, 850 Republican Street, Brotman Building Room 453, Seattle, WA 98109, USA.
Andrea LeonardDepartment of Mechanical Engineering, 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, 850 Republican Street, Brotman Building Room 453, Seattle, WA 98109, USA.
Lihua SunDepartment 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, 850 Republican Street, Brotman Building Room 453, Seattle, WA 98109, USA; Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China.
Karin A FischerDepartment of Biochemistry, University of Washington, Seattle, WA 98109, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, 850 Republican Street, Brotman Building Room 453, Seattle, WA 98109, USA.
Yuliang WangInstitute for Stem Cell and Regenerative Medicine, University of Washington, 850 Republican Street, Brotman Building Room 453, Seattle, WA 98109, USA; Paul G. Allen School of Computer Science and Engineering, University of Washington, Seattle, WA 98109, USA.
Julia RitterhoffMitochondria and Metabolism Center, University of Washington, Seattle, WA 98109, USA; Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA 98109, USA.
Limei ZhaoDepartment 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, 850 Republican Street, Brotman Building Room 453, Seattle, WA 98109, USA.
Stephen C KolwiczMitochondria and Metabolism Center, University of Washington, Seattle, WA 98109, USA; Department of Anesthesiology and Pain Medicine, 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, 850 Republican Street, Brotman Building Room 453, 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, 850 Republican Street, Brotman Building Room 453, Seattle, WA 98109, USA.
Nathan J SniadeckiDepartment of Mechanical Engineering, 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, 850 Republican Street, Brotman Building Room 453, Seattle, WA 98109, USA.
Rong TianMitochondria and Metabolism Center, University of Washington, Seattle, WA 98109, USA; Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA 98109, USA.
Hannele Ruohola-BakerDepartment of Biochemistry, University of Washington, Seattle, WA 98109, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, 850 Republican Street, Brotman Building Room 453, Seattle, WA 98109, USA.
Haodong XuDepartment 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, 850 Republican Street, Brotman Building Room 453, 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, 850 Republican Street, Brotman Building Room 453, Seattle, WA 98109, USA. Electronic address: murry@uw.edu.
University of Washington · USHarbin Medical University · CN

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
University of Washington Center for Nuclear Organization and FunctionU54DK107979 · NIDDK · UNIVERSITY OF WASHINGTON · PI NOBLE, WILLIAM STAFFORD, SHENDURE, JAY ASHOK · 2015 to 2019
$11.8M
Engineered Stem Cells for Cardiac RepairR01HL128368 · NHLBI · UNIVERSITY OF WASHINGTON · PI REGNIER, MICHAEL · 2018 to 2025
$6.1M
Primate Heart RegenerationR01HL128362 · NHLBI · UNIVERSITY OF WASHINGTON · PI MURRY, CHARLES E · 2016 to 2019
$3.5M
Mechanisms of Cell-Based Heart RegenerationR01HL146868 · NHLBI · UNIVERSITY OF WASHINGTON · PI MURRY, CHARLES E, SNIADECKI, NATHAN JOHN · 2019 to 2022
$3.5M
Fatty acid oxidation suppresses cardiac hypertrophyR01HL129510 · NHLBI · UNIVERSITY OF WASHINGTON · PI TIAN, RONG · 2015 to 2018
$2.8M
NHLBI NIH HHS P01 HL094374NHLBI NIH HHS R01 HL128362NHLBI NIH HHS R01 HL128368NHLBI NIH HHS R01 HL129510NHLBI NIH HHS R01 HL146868NIDDK NIH HHS U54 DK107979NIGMS NIH HHS P01 GM081619
6 · The paper itself

Abstract

Although human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) have emerged as a novel platform for heart regeneration, disease modeling, and drug screening, their immaturity significantly hinders their application. A hallmark of postnatal cardiomyocyte maturation is the metabolic substrate switch from glucose to fatty acids. We hypothesized that fatty acid supplementation would enhance hPSC-CM maturation. Fatty acid treatment induces cardiomyocyte hypertrophy and significantly increases cardiomyocyte force production. The improvement in force generation is accompanied by enhanced calcium transient peak height and kinetics, and by increased action potential upstroke velocity and membrane capacitance. Fatty acids also enhance mitochondrial respiratory reserve capacity. RNA sequencing showed that fatty acid treatment upregulates genes involved in fatty acid β-oxidation and downregulates genes in lipid synthesis. Signal pathway analyses reveal that fatty acid treatment results in phosphorylation and activation of multiple intracellular kinases. Thus, fatty acids increase human cardiomyocyte hypertrophy, force generation, calcium dynamics, action potential upstroke velocity, and oxidative capacity. This enhanced maturation should facilitate hPSC-CM usage for cell therapy, disease modeling, and drug/toxicity screens.

Indexed as

Cell DifferentiationCalciumCarnitineCell LineDietary SupplementsFatty AcidsHumansInduced Pluripotent Stem CellsKineticsMembrane PotentialsMitochondria, HeartMuscle ContractionMyocytes, CardiacOxidation-ReductionOxidative PhosphorylationSignal TransductionCalciumCarnitineFatty Acidscardiomyocyte maturationembryonic stem cellsfatty acidsinduced pluripotent stem cellsmetabolism

Identifiers

PMID31564645
PMCPMC6829750
OpenAlexW2975681149

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.