Transcriptome Profiling of Patient-Specific Human iPSC-Cardiomyocytes Predicts Individual Drug Safety and Efficacy Responses In Vitro

Elena Matsa, Paul W. Burridge, Kun Hsing Yu, John H. Ahrens, Vittavat Termglinchan, Haodi Wu, Chun Liu, Praveen Shukla, Nazish Sayed, Jared M. Churko, Ningyi Shao, Nicole A. Woo, Alexander S. Chao, Joseph D. Gold, Ioannis Karakikes, Michael P. Snyder, Joseph C. Wu

Research output: Contribution to journalArticlepeer-review

112 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)311-325
Number of pages15
JournalCell Stem Cell
Issue number3
StatePublished - Sep 1 2016


  • cardiomyocytes
  • induced pluripotent stem cells
  • personalized drug safety and efficacy
  • precision medicine

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Cell Biology


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