ArticleCirculation research2014
Human induced pluripotent stem cell-derived cardiomyocytes as an in vitro model for coxsackievirus B3-induced myocarditis and antiviral drug screening platform.
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Article in Circulation research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
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88citing papers in PubMed
8.7field-weighted citation impact, top 2% of its field
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Who cites it
88 citing papers in PubMed, 150 citations in OpenAlex.
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- Multi-lineage heart-chip models drug cardiotoxicity and enhances maturation of human stem cell-derived cardiovascular cells.Lab on a chip · 2024Article
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- Animal models and animal-free innovations for cardiovascular research: current status and routes to be explored. Consensus document of the ESC Working Group on Myocardial Function and the ESC Working Group on Cellular Biology of the Heart.Cardiovascular research · 2022Article
- Merits of hiPSC-Derived Cardiomyocytes for In Vitro Research and Testing Drug Toxicity.Biomedicines · 2022Article
28 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 1 institution in 1 country.
Arun SharmaFrom the Department of Medicine, Division of Cardiology (A.S., R.H., P.W.B., K.R., J.M.C., H.W., K.I.S., E.M., A.C.S., Y.C., A.E., S.D., P.L., S.M.W., J.C.W.), Institute for Stem Cell Biology and Regenerative Medicine (A.S., R.H., P.W.B., K.R., J.M.C., H.W., K.I.S., E.M., A.C.S., Y.C., A.E., S.D., P.L., S.M.W., J.C.W.), Stanford Cardiovascular Institute (A.S., R.H., P.W.B., K.R., J.M.C., H.W., K.I.S., E.M., A.C.S., Y.C., A.E., S.D., P.L., K.R.-H., S.M.W., J.C.W.), Department of Biology (A.S., R.H., K.R.-H.), Department of Microbiology and Immunology (C.M., J.E.C.), and Department of Radiology, Molecular Imaging Program (J.C.W.), Stanford University School of Medicine, CA.
Caleb MarceauFrom the Department of Medicine, Division of Cardiology (A.S., R.H., P.W.B., K.R., J.M.C., H.W., K.I.S., E.M., A.C.S., Y.C., A.E., S.D., P.L., S.M.W., J.C.W.), Institute for Stem Cell Biology and Regenerative Medicine (A.S., R.H., P.W.B., K.R., J.M.C., H.W., K.I.S., E.M., A.C.S., Y.C., A.E., S.D., P.L., S.M.W., J.C.W.), Stanford Cardiovascular Institute (A.S., R.H., P.W.B., K.R., J.M.C., H.W., K.I.S., E.M., A.C.S., Y.C., A.E., S.D., P.L., K.R.-H., S.M.W., J.C.W.), Department of Biology (A.S., R.H., K.R.-H.), Department of Microbiology and Immunology (C.M., J.E.C.), and Department of Radiology, Molecular Imaging Program (J.C.W.), Stanford University School of Medicine, CA.
Ryoko HamaguchiFrom the Department of Medicine, Division of Cardiology (A.S., R.H., P.W.B., K.R., J.M.C., H.W., K.I.S., E.M., A.C.S., Y.C., A.E., S.D., P.L., S.M.W., J.C.W.), Institute for Stem Cell Biology and Regenerative Medicine (A.S., R.H., P.W.B., K.R., J.M.C., H.W., K.I.S., E.M., A.C.S., Y.C., A.E., S.D., P.L., S.M.W., J.C.W.), Stanford Cardiovascular Institute (A.S., R.H., P.W.B., K.R., J.M.C., H.W., K.I.S., E.M., A.C.S., Y.C., A.E., S.D., P.L., K.R.-H., S.M.W., J.C.W.), Department of Biology (A.S., R.H., K.R.-H.), Department of Microbiology and Immunology (C.M., J.E.C.), and Department of Radiology, Molecular Imaging Program (J.C.W.), Stanford University School of Medicine, CA.
Paul W BurridgeFrom the Department of Medicine, Division of Cardiology (A.S., R.H., P.W.B., K.R., J.M.C., H.W., K.I.S., E.M., A.C.S., Y.C., A.E., S.D., P.L., S.M.W., J.C.W.), Institute for Stem Cell Biology and Regenerative Medicine (A.S., R.H., P.W.B., K.R., J.M.C., H.W., K.I.S., E.M., A.C.S., Y.C., A.E., S.D., P.L., S.M.W., J.C.W.), Stanford Cardiovascular Institute (A.S., R.H., P.W.B., K.R., J.M.C., H.W., K.I.S., E.M., A.C.S., Y.C., A.E., S.D., P.L., K.R.-H., S.M.W., J.C.W.), Department of Biology (A.S., R.H., K.R.-H.), Department of Microbiology and Immunology (C.M., J.E.C.), and Department of Radiology, Molecular Imaging Program (J.C.W.), Stanford University School of Medicine, CA.
Kuppusamy RajarajanFrom the Department of Medicine, Division of Cardiology (A.S., R.H., P.W.B., K.R., J.M.C., H.W., K.I.S., E.M., A.C.S., Y.C., A.E., S.D., P.L., S.M.W., J.C.W.), Institute for Stem Cell Biology and Regenerative Medicine (A.S., R.H., P.W.B., K.R., J.M.C., H.W., K.I.S., E.M., A.C.S., Y.C., A.E., S.D., P.L., S.M.W., J.C.W.), Stanford Cardiovascular Institute (A.S., R.H., P.W.B., K.R., J.M.C., H.W., K.I.S., E.M., A.C.S., Y.C., A.E., S.D., P.L., K.R.-H., S.M.W., J.C.W.), Department of Biology (A.S., R.H., K.R.-H.), Department of Microbiology and Immunology (C.M., J.E.C.), and Department of Radiology, Molecular Imaging Program (J.C.W.), Stanford University School of Medicine, CA.
Jared M ChurkoFrom the Department of Medicine, Division of Cardiology (A.S., R.H., P.W.B., K.R., J.M.C., H.W., K.I.S., E.M., A.C.S., Y.C., A.E., S.D., P.L., S.M.W., J.C.W.), Institute for Stem Cell Biology and Regenerative Medicine (A.S., R.H., P.W.B., K.R., J.M.C., H.W., K.I.S., E.M., A.C.S., Y.C., A.E., S.D., P.L., S.M.W., J.C.W.), Stanford Cardiovascular Institute (A.S., R.H., P.W.B., K.R., J.M.C., H.W., K.I.S., E.M., A.C.S., Y.C., A.E., S.D., P.L., K.R.-H., S.M.W., J.C.W.), Department of Biology (A.S., R.H., K.R.-H.), Department of Microbiology and Immunology (C.M., J.E.C.), and Department of Radiology, Molecular Imaging Program (J.C.W.), Stanford University School of Medicine, CA.
Haodi WuFrom the Department of Medicine, Division of Cardiology (A.S., R.H., P.W.B., K.R., J.M.C., H.W., K.I.S., E.M., A.C.S., Y.C., A.E., S.D., P.L., S.M.W., J.C.W.), Institute for Stem Cell Biology and Regenerative Medicine (A.S., R.H., P.W.B., K.R., J.M.C., H.W., K.I.S., E.M., A.C.S., Y.C., A.E., S.D., P.L., S.M.W., J.C.W.), Stanford Cardiovascular Institute (A.S., R.H., P.W.B., K.R., J.M.C., H.W., K.I.S., E.M., A.C.S., Y.C., A.E., S.D., P.L., K.R.-H., S.M.W., J.C.W.), Department of Biology (A.S., R.H., K.R.-H.), Department of Microbiology and Immunology (C.M., J.E.C.), and Department of Radiology, Molecular Imaging Program (J.C.W.), Stanford University School of Medicine, CA.
Karim I SallamFrom the Department of Medicine, Division of Cardiology (A.S., R.H., P.W.B., K.R., J.M.C., H.W., K.I.S., E.M., A.C.S., Y.C., A.E., S.D., P.L., S.M.W., J.C.W.), Institute for Stem Cell Biology and Regenerative Medicine (A.S., R.H., P.W.B., K.R., J.M.C., H.W., K.I.S., E.M., A.C.S., Y.C., A.E., S.D., P.L., S.M.W., J.C.W.), Stanford Cardiovascular Institute (A.S., R.H., P.W.B., K.R., J.M.C., H.W., K.I.S., E.M., A.C.S., Y.C., A.E., S.D., P.L., K.R.-H., S.M.W., J.C.W.), Department of Biology (A.S., R.H., K.R.-H.), Department of Microbiology and Immunology (C.M., J.E.C.), and Department of Radiology, Molecular Imaging Program (J.C.W.), Stanford University School of Medicine, CA.
Elena MatsaFrom the Department of Medicine, Division of Cardiology (A.S., R.H., P.W.B., K.R., J.M.C., H.W., K.I.S., E.M., A.C.S., Y.C., A.E., S.D., P.L., S.M.W., J.C.W.), Institute for Stem Cell Biology and Regenerative Medicine (A.S., R.H., P.W.B., K.R., J.M.C., H.W., K.I.S., E.M., A.C.S., Y.C., A.E., S.D., P.L., S.M.W., J.C.W.), Stanford Cardiovascular Institute (A.S., R.H., P.W.B., K.R., J.M.C., H.W., K.I.S., E.M., A.C.S., Y.C., A.E., S.D., P.L., K.R.-H., S.M.W., J.C.W.), Department of Biology (A.S., R.H., K.R.-H.), Department of Microbiology and Immunology (C.M., J.E.C.), and Department of Radiology, Molecular Imaging Program (J.C.W.), Stanford University School of Medicine, CA.
Anthony C SturzuFrom the Department of Medicine, Division of Cardiology (A.S., R.H., P.W.B., K.R., J.M.C., H.W., K.I.S., E.M., A.C.S., Y.C., A.E., S.D., P.L., S.M.W., J.C.W.), Institute for Stem Cell Biology and Regenerative Medicine (A.S., R.H., P.W.B., K.R., J.M.C., H.W., K.I.S., E.M., A.C.S., Y.C., A.E., S.D., P.L., S.M.W., J.C.W.), Stanford Cardiovascular Institute (A.S., R.H., P.W.B., K.R., J.M.C., H.W., K.I.S., E.M., A.C.S., Y.C., A.E., S.D., P.L., K.R.-H., S.M.W., J.C.W.), Department of Biology (A.S., R.H., K.R.-H.), Department of Microbiology and Immunology (C.M., J.E.C.), and Department of Radiology, Molecular Imaging Program (J.C.W.), Stanford University School of Medicine, CA.
Yonglu CheFrom the Department of Medicine, Division of Cardiology (A.S., R.H., P.W.B., K.R., J.M.C., H.W., K.I.S., E.M., A.C.S., Y.C., A.E., S.D., P.L., S.M.W., J.C.W.), Institute for Stem Cell Biology and Regenerative Medicine (A.S., R.H., P.W.B., K.R., J.M.C., H.W., K.I.S., E.M., A.C.S., Y.C., A.E., S.D., P.L., S.M.W., J.C.W.), Stanford Cardiovascular Institute (A.S., R.H., P.W.B., K.R., J.M.C., H.W., K.I.S., E.M., A.C.S., Y.C., A.E., S.D., P.L., K.R.-H., S.M.W., J.C.W.), Department of Biology (A.S., R.H., K.R.-H.), Department of Microbiology and Immunology (C.M., J.E.C.), and Department of Radiology, Molecular Imaging Program (J.C.W.), Stanford University School of Medicine, CA.
Antje EbertFrom the Department of Medicine, Division of Cardiology (A.S., R.H., P.W.B., K.R., J.M.C., H.W., K.I.S., E.M., A.C.S., Y.C., A.E., S.D., P.L., S.M.W., J.C.W.), Institute for Stem Cell Biology and Regenerative Medicine (A.S., R.H., P.W.B., K.R., J.M.C., H.W., K.I.S., E.M., A.C.S., Y.C., A.E., S.D., P.L., S.M.W., J.C.W.), Stanford Cardiovascular Institute (A.S., R.H., P.W.B., K.R., J.M.C., H.W., K.I.S., E.M., A.C.S., Y.C., A.E., S.D., P.L., K.R.-H., S.M.W., J.C.W.), Department of Biology (A.S., R.H., K.R.-H.), Department of Microbiology and Immunology (C.M., J.E.C.), and Department of Radiology, Molecular Imaging Program (J.C.W.), Stanford University School of Medicine, CA.
Sebastian DieckeFrom the Department of Medicine, Division of Cardiology (A.S., R.H., P.W.B., K.R., J.M.C., H.W., K.I.S., E.M., A.C.S., Y.C., A.E., S.D., P.L., S.M.W., J.C.W.), Institute for Stem Cell Biology and Regenerative Medicine (A.S., R.H., P.W.B., K.R., J.M.C., H.W., K.I.S., E.M., A.C.S., Y.C., A.E., S.D., P.L., S.M.W., J.C.W.), Stanford Cardiovascular Institute (A.S., R.H., P.W.B., K.R., J.M.C., H.W., K.I.S., E.M., A.C.S., Y.C., A.E., S.D., P.L., K.R.-H., S.M.W., J.C.W.), Department of Biology (A.S., R.H., K.R.-H.), Department of Microbiology and Immunology (C.M., J.E.C.), and Department of Radiology, Molecular Imaging Program (J.C.W.), Stanford University School of Medicine, CA.
Ping LiangFrom the Department of Medicine, Division of Cardiology (A.S., R.H., P.W.B., K.R., J.M.C., H.W., K.I.S., E.M., A.C.S., Y.C., A.E., S.D., P.L., S.M.W., J.C.W.), Institute for Stem Cell Biology and Regenerative Medicine (A.S., R.H., P.W.B., K.R., J.M.C., H.W., K.I.S., E.M., A.C.S., Y.C., A.E., S.D., P.L., S.M.W., J.C.W.), Stanford Cardiovascular Institute (A.S., R.H., P.W.B., K.R., J.M.C., H.W., K.I.S., E.M., A.C.S., Y.C., A.E., S.D., P.L., K.R.-H., S.M.W., J.C.W.), Department of Biology (A.S., R.H., K.R.-H.), Department of Microbiology and Immunology (C.M., J.E.C.), and Department of Radiology, Molecular Imaging Program (J.C.W.), Stanford University School of Medicine, CA.
Kristy Red-HorseFrom the Department of Medicine, Division of Cardiology (A.S., R.H., P.W.B., K.R., J.M.C., H.W., K.I.S., E.M., A.C.S., Y.C., A.E., S.D., P.L., S.M.W., J.C.W.), Institute for Stem Cell Biology and Regenerative Medicine (A.S., R.H., P.W.B., K.R., J.M.C., H.W., K.I.S., E.M., A.C.S., Y.C., A.E., S.D., P.L., S.M.W., J.C.W.), Stanford Cardiovascular Institute (A.S., R.H., P.W.B., K.R., J.M.C., H.W., K.I.S., E.M., A.C.S., Y.C., A.E., S.D., P.L., K.R.-H., S.M.W., J.C.W.), Department of Biology (A.S., R.H., K.R.-H.), Department of Microbiology and Immunology (C.M., J.E.C.), and Department of Radiology, Molecular Imaging Program (J.C.W.), Stanford University School of Medicine, CA.
Jan E CaretteFrom the Department of Medicine, Division of Cardiology (A.S., R.H., P.W.B., K.R., J.M.C., H.W., K.I.S., E.M., A.C.S., Y.C., A.E., S.D., P.L., S.M.W., J.C.W.), Institute for Stem Cell Biology and Regenerative Medicine (A.S., R.H., P.W.B., K.R., J.M.C., H.W., K.I.S., E.M., A.C.S., Y.C., A.E., S.D., P.L., S.M.W., J.C.W.), Stanford Cardiovascular Institute (A.S., R.H., P.W.B., K.R., J.M.C., H.W., K.I.S., E.M., A.C.S., Y.C., A.E., S.D., P.L., K.R.-H., S.M.W., J.C.W.), Department of Biology (A.S., R.H., K.R.-H.), Department of Microbiology and Immunology (C.M., J.E.C.), and Department of Radiology, Molecular Imaging Program (J.C.W.), Stanford University School of Medicine, CA.
Sean M WuFrom the Department of Medicine, Division of Cardiology (A.S., R.H., P.W.B., K.R., J.M.C., H.W., K.I.S., E.M., A.C.S., Y.C., A.E., S.D., P.L., S.M.W., J.C.W.), Institute for Stem Cell Biology and Regenerative Medicine (A.S., R.H., P.W.B., K.R., J.M.C., H.W., K.I.S., E.M., A.C.S., Y.C., A.E., S.D., P.L., S.M.W., J.C.W.), Stanford Cardiovascular Institute (A.S., R.H., P.W.B., K.R., J.M.C., H.W., K.I.S., E.M., A.C.S., Y.C., A.E., S.D., P.L., K.R.-H., S.M.W., J.C.W.), Department of Biology (A.S., R.H., K.R.-H.), Department of Microbiology and Immunology (C.M., J.E.C.), and Department of Radiology, Molecular Imaging Program (J.C.W.), Stanford University School of Medicine, CA. joewu@stanford.edu smwu@stanford.edu.
Joseph C WuFrom the Department of Medicine, Division of Cardiology (A.S., R.H., P.W.B., K.R., J.M.C., H.W., K.I.S., E.M., A.C.S., Y.C., A.E., S.D., P.L., S.M.W., J.C.W.), Institute for Stem Cell Biology and Regenerative Medicine (A.S., R.H., P.W.B., K.R., J.M.C., H.W., K.I.S., E.M., A.C.S., Y.C., A.E., S.D., P.L., S.M.W., J.C.W.), Stanford Cardiovascular Institute (A.S., R.H., P.W.B., K.R., J.M.C., H.W., K.I.S., E.M., A.C.S., Y.C., A.E., S.D., P.L., K.R.-H., S.M.W., J.C.W.), Department of Biology (A.S., R.H., K.R.-H.), Department of Microbiology and Immunology (C.M., J.E.C.), and Department of Radiology, Molecular Imaging Program (J.C.W.), Stanford University School of Medicine, CA. joewu@stanford.edu smwu@stanford.edu.
S.P.E.C.I.E.S. · US
Funding
MULTIDISCIPLINARY RESEARCH TRAINING IN CARDIOLOGYT32HL007208 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI Patrick Thomas Ellinor, David E Sosnovik · 1985 to 2026
$16.1MMOLECULAR BASIS OF HOST-PARASITE INTERACTIONT32AI007328 · NIAID · STANFORD UNIVERSITY · PI JUSTIN L SONNENBURG · 1987 to 2026
$11.9MInduced pluripotent stem cells in the understanding and treatment of heart diseaseU01HL099776 · NHLBI · STANFORD UNIVERSITY · PI LONGAKER, MICHAEL T, WU, JOSEPH C. · 2009 to 2015
$8.2MHuman Induced Pluripotent Stem Cells for Cardiovascular Disease ModelingR01HL113006 · NHLBI · STANFORD UNIVERSITY · PI WU, JOSEPH C. · 2012 to 2025
$6.8MVECTOR COREP30NS069375 · NINDS · STANFORD UNIVERSITY · PI STEINBERG, GARY K · 2011 to 2019
$6.3MGeneration of functional organs via developmental chimerismDP2OD004411 · OD · STANFORD UNIVERSITY · PI WU, SEAN M · 2008 to 2008
$2.5MGenetic approaches to discover host factors critical to dengue virus infectionDP2AI104557 · NIAID · STANFORD UNIVERSITY · PI CARETTE, JAN E · 2012 to 2012
$2.3MNHLBI NIH HHS R01 HL113006NHLBI NIH HHS T32 HL007208NHLBI NIH HHS U01 HL099776NIAID NIH HHS DP2 AI104557NIAID NIH HHS T32 AI007328NIH HHS DP2 OD004411NINDS NIH HHS NS069375
Abstract
rationaleViral myocarditis is a life-threatening illness that may lead to heart failure or cardiac arrhythmias. A major causative agent for viral myocarditis is the B3 strain of coxsackievirus, a positive-sense RNA enterovirus. However, human cardiac tissues are difficult to procure in sufficient enough quantities for studying the mechanisms of cardiac-specific viral infection.
objectiveThis study examined whether human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) could be used to model the pathogenic processes of coxsackievirus-induced viral myocarditis and to screen antiviral therapeutics for efficacy. METHODS AND
resultshiPSC-CMs were infected with a luciferase-expressing coxsackievirus B3 strain (CVB3-Luc). Brightfield microscopy, immunofluorescence, and calcium imaging were used to characterize virally infected hiPSC-CMs for alterations in cellular morphology and calcium handling. Viral proliferation in hiPSC-CMs was quantified using bioluminescence imaging. Antiviral compounds including interferonβ1, ribavirin, pyrrolidine dithiocarbamate, and fluoxetine were tested for their capacity to abrogate CVB3-Luc proliferation in hiPSC-CMs in vitro. The ability of these compounds to reduce CVB3-Luc proliferation in hiPSC-CMs was consistent with reported drug effects in previous studies. Mechanistic analyses via gene expression profiling of hiPSC-CMs infected with CVB3-Luc revealed an activation of viral RNA and protein clearance pathways after interferonβ1 treatment.
conclusionsThis study demonstrates that hiPSC-CMs express the coxsackievirus and adenovirus receptor, are susceptible to coxsackievirus infection, and can be used to predict antiviral drug efficacy. Our results suggest that the hiPSC-CM/CVB3-Luc assay is a sensitive platform that can screen novel antiviral therapeutics for their effectiveness in a high-throughput fashion.
Indexed as
Models, CardiovascularAntiviral AgentsCalciumCell ProliferationCells, CulturedDrug Evaluation, PreclinicalEnterovirus B, HumanEnterovirus InfectionsHumansIn Vitro TechniquesMyocarditisMyocytes, CardiacPluripotent Stem CellsRNA, ViralTreatment OutcomeAntiviral AgentsCalciumRNA, Viralmyocarditismyocytes, cardiacstem cells
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