Human Induced Pluripotent Stem Cell (hiPSC)-Derived Cells to Assess Drug Cardiotoxicity: Opportunities and Problems

Tarek Magdy, Adam J.T. Schuldt, Joseph C. Wu, Daniel Bernstein, Paul W. Burridge

Research output: Contribution to journalReview articlepeer-review

39 Scopus citations

Abstract

Billions of US dollars are invested every year by the pharmaceutical industry in drug development, with the aim of introducing new drugs that are effective and have minimal side effects. Thirty percent of in-pipeline drugs are excluded in an early phase of preclinical and clinical screening owing to cardiovascular safety concerns, and several lead molecules that pass the early safety screening make it to market but are later withdrawn owing to severe cardiac side effects. Although the current drug safety screening methodologies can identify some cardiotoxic drug candidates, they cannot accurately represent the human heart in many aspects, including genomics, transcriptomics, and patient- or population-specific cardiotoxicity. Despite some limitations, human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are a powerful and evolving technology that has been shown to recapitulate many attributes of human cardiomyocytes and their drug responses. In this review, we discuss the potential impact of the inclusion of the hiPSC-CM platform in premarket candidate drug screening.

Original languageEnglish (US)
Pages (from-to)83-103
Number of pages21
JournalAnnual Review of Pharmacology and Toxicology
Volume58
DOIs
StatePublished - Jan 6 2018

Keywords

  • cardiac
  • cardiomyocyte
  • cardiotoxicity
  • chemotherapy
  • differentiation
  • human induced pluripotent stem cells
  • pharmacogenomics

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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