ArticleCell stem cell2016
Transcriptome Profiling of Patient-Specific Human iPSC-Cardiomyocytes Predicts Individual Drug Safety and Efficacy Responses In Vitro.
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Article in Cell stem cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers.
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95citing papers in PubMed
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Who cites it
95 citing papers in PubMed, 159 citations in OpenAlex.
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- From aging biology to cardiac biotechnology: emerging platforms for modeling cardiac aging.JCI insight · 2026Review
- Human thyroid organoids: tools for understanding thyroid diseases and development.Nature reviews. Endocrinology · 2026Review
- Sphingosine-1-phosphate receptor 1 signaling stimulates human pluripotent stem cell-derived cardiomyocyte differentiation and maturation.Experimental & molecular medicine · 2026Article
- Fluorescence-lifetime optical electrophysiology in contracting cardiomyocytes.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Advanced physiological maturation of human iPSC-derived cardiomyocytes using an algorithm-directed optimization of defined media components.Nature communications · 2026Article
- Protocol to generate immunocompetent human heart-macrophage assembloids for the study of immune-cardiac interactions.STAR protocols · 2026Article
- Quantifying HiPSC-CM structural organization at scale with deep learning-enhanced SarcGraph.PLoS computational biology · 2025Article
- Engineering the next generation of allogeneic CAR cells: iPSCs as a scalable and editable platform.Stem cell reports · 2025Review
- Clinical trials in-a-dish for cardiovascular medicine.European heart journal · 2024Review
- A Novel Stem Cell Model to Study Preeclampsia Endothelial Dysfunction.Reproductive sciences (Thousand Oaks, Calif.) · 2024Article
- Immune response caused by M1 macrophages elicits atrial fibrillation-like phenotypes in coculture model with isogenic hiPSC-derived cardiomyocytes.Stem cell research & therapy · 2024Article
- Cardiovascular Toxicity in Cancer Therapy: Protecting the Heart while Combating Cancer.Current cardiology reports · 2024Review
- Informing Hazard Identification and Risk Characterization of Environmental Chemicals by Combining Transcriptomic and Functional Data from Human-Induced Pluripotent Stem-Cell-Derived Cardiomyocytes.Chemical research in toxicology · 2024Article
- Advances in induced pluripotent stem cell-derived cardiac myocytes: technological breakthroughs, key discoveries and new applications.The Journal of physiology · 2024Review
- Computational approaches identify a transcriptomic fingerprint of drug-induced structural cardiotoxicity.Cell biology and toxicology · 2024Article
- Sex-Based Mechanisms of Cardiac Development and Function: Applications for Induced-Pluripotent Stem Cell Derived-Cardiomyocytes.International journal of molecular sciences · 2024Review
- Article
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Authors and funding
17 authors at 4 institutions in 1 country.
Elena MatsaStanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; Departments of Medicine and Radiology, Stanford University School of Medicine, Stanford, CA 94305, USA; Institute of Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: ematsa@stanford.edu.
Paul W BurridgeStanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; Departments of Medicine and Radiology, Stanford University School of Medicine, Stanford, CA 94305, USA; Institute of Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA; Center for Pharmacogenomics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Kun-Hsing YuDepartment of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA; Biomedical Informatics Training Program, Stanford University School of Medicine, Stanford, CA 94305, USA.
John H AhrensStanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
Vittavat TermglinchanStanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; Departments of Medicine and Radiology, Stanford University School of Medicine, Stanford, CA 94305, USA; Institute of Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Haodi WuStanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; Departments of Medicine and Radiology, Stanford University School of Medicine, Stanford, CA 94305, USA; Institute of Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Chun LiuStanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; Departments of Medicine and Radiology, Stanford University School of Medicine, Stanford, CA 94305, USA; Institute of Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Praveen ShuklaStanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; Departments of Medicine and Radiology, Stanford University School of Medicine, Stanford, CA 94305, USA; Institute of Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Nazish SayedStanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; Departments of Medicine and Radiology, Stanford University School of Medicine, Stanford, CA 94305, USA; Institute of Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Jared M ChurkoStanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; Departments of Medicine and Radiology, Stanford University School of Medicine, Stanford, CA 94305, USA; Institute of Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Ningyi ShaoStanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; Departments of Medicine and Radiology, Stanford University School of Medicine, Stanford, CA 94305, USA; Institute of Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Nicole A WooStanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
Alexander S ChaoStanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
Joseph D GoldStanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
Ioannis KarakikesStanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; Departments of Medicine and Radiology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Michael P SnyderDepartment of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Joseph C WuStanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; Departments of Medicine and Radiology, Stanford University School of Medicine, Stanford, CA 94305, USA; Institute of Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: joewu@stanford.edu.
Cardiovascular Institute of the South · USStanford University · USCalifornia Institute for Regenerative Medicine · USNorthwestern University · US
Funding
Tumor Environment and Metastasis (TEAM) Research ProgramP30CA060553 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI LEONIDAS C. PLATANIAS · 1993 to 2026
$153.9MProject 3: Effect of Age and Longevity Genes on Epigenomic MechanismsP01GM099130 · NIGMS · STANFORD UNIVERSITY · PI SNYDER, MICHAEL P. · 2011 to 2015
$11.4MiPSC Derived EC as Surrogates Using Pulmonary Hypertension as a Prototype DiseaseU01HL107393 · NHLBI · STANFORD UNIVERSITY · PI RABINOVITCH, MARLENE, SNYDER, MICHAEL P. · 2011 to 2015
$8.7MElucidating Mechanism of Cardiac Fibrosis with Cell Village of Pooled Human iPSCsR01HL130020 · NHLBI · STANFORD UNIVERSITY · PI Ronglih Liao, MARK MERCOLA · 2016 to 2026
$7.3MHuman Induced Pluripotent Stem Cells for Cardiovascular Disease ModelingR01HL113006 · NHLBI · STANFORD UNIVERSITY · PI WU, JOSEPH C. · 2012 to 2025
$6.8MGenome Editing of Human iPSCs to Study Inherited Hypertrophic CardiomyopathyR01HL126527 · NHLBI · STANFORD UNIVERSITY · PI QI, LEI STANLEY, WU, JOSEPH C. · 2015 to 2022
$5.4MModeling Susceptibility to Chemotherapy-Induced Cardiotoxicity Using Human iPSCsR01HL123968 · NHLBI · STANFORD UNIVERSITY · PI QUERTERMOUS, THOMAS, WU, JOSEPH C. · 2014 to 2021
$4.8MA Systems Biology Approach to Study Cardiac Arrhythmias: iPS Cells and In Silico ModelingR01HL128170 · NHLBI · STANFORD UNIVERSITY · PI ALTMAN, RUSS BIAGIO, CLANCY, COLLEEN E · 2015 to 2018
$3.0MRobust, Generalizable, and Fair Machine Learning Models for BiomedicineR35GM142879 · NIGMS · HARVARD MEDICAL SCHOOL · PI YU, KUN-HSING · 2021 to 2025
$2.4MModeling the role of the genome in chemotherapy induced cardiotoxicity using iPSCR00HL121177 · NHLBI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI BURRIDGE, PAUL W. · 2015 to 2017
$743kmiR-152: A Novel Regulator of Diabetic CardiomyopathyK99HL104002 · NHLBI · STANFORD UNIVERSITY · PI KARAKIKES, IOANNIS · 2012 to 2013
$208kModeling the role of the genome in chemotherapy induced cardiotoxicity using iPSCK99HL121177 · NHLBI · STANFORD UNIVERSITY · PI BURRIDGE, PAUL W. · 2014 to 2014
$89kAmerican Heart Association-American Stroke Association 14BGIA20480329NCI NIH HHS P30 CA060553NHLBI NIH HHS K99 HL104002NHLBI NIH HHS K99 HL121177NHLBI NIH HHS R00 HL121177NHLBI NIH HHS R01 HL113006NHLBI NIH HHS R01 HL123968NHLBI NIH HHS R01 HL126527NHLBI NIH HHS R01 HL128170NHLBI NIH HHS R01 HL130020NHLBI NIH HHS U01 HL107393NIGMS NIH HHS P01 GM099130NIGMS NIH HHS R35 GM142879
Abstract
Understanding individual susceptibility to drug-induced cardiotoxicity is key to improving patient safety and preventing drug attrition. Human induced pluripotent stem cells (hiPSCs) enable the study of pharmacological and toxicological responses in patient-specific cardiomyocytes (CMs) and may serve as preclinical platforms for precision medicine. Transcriptome profiling in hiPSC-CMs from seven individuals lacking known cardiovascular disease-associated mutations and in three isogenic human heart tissue and hiPSC-CM pairs showed greater inter-patient variation than intra-patient variation, verifying that reprogramming and differentiation preserve patient-specific gene expression, particularly in metabolic and stress-response genes. Transcriptome-based toxicology analysis predicted and risk-stratified patient-specific susceptibility to cardiotoxicity, and functional assays in hiPSC-CMs using tacrolimus and rosiglitazone, drugs targeting pathways predicted to produce cardiotoxicity, validated inter-patient differential responses. CRISPR/Cas9-mediated pathway correction prevented drug-induced cardiotoxicity. Our data suggest that hiPSC-CMs can be used in vitro to predict and validate patient-specific drug safety and efficacy, potentially enabling future clinical approaches to precision medicine.
Indexed as
Gene Expression ProfilingCell DeathCRISPR-Cas SystemsGene EditingGenome, HumanHeart VentriclesHumansInduced Pluripotent Stem CellsInverted Repeat SequencesMyocytes, CardiacRosiglitazoneTacrolimusThiazolidinedionesTreatment OutcomeRosiglitazoneTacrolimusThiazolidinedionescardiomyocytesinduced pluripotent stem cellspersonalized drug safety and efficacyprecision medicine
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