Unlocking personalized biomedicine and drug discovery with human induced pluripotent stem cell-derived cardiomyocytes: Fit for purpose or forever elusive?

Tessa De Korte, Puspita A. Katili, Nurul A.N. Mohd Yusof, Berend J. Van Meer, Umber Saleem, Francis L. Burton, Godfrey L. Smith, Peter Clements, Christine L. Mummery, Thomas Eschenhagen, Arne Hansen, Chris Denning

Research output: Contribution to journalReview articlepeer-review

19 Citations (Scopus)

Abstract

In recent decades, drug development costs have increased by approximately a hundredfold, and yet about 1 in 7 licensed drugs are withdrawn from the market, often due to cardiotoxicity. This review considers whether technologies using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) could complement existing assays to improve discovery and safety while reducing socioeconomic costs and assisting with regulatory guidelines on cardiac safety assessments. We draw on lessons from our own work to suggest a panel of 12 drugs that will be useful in testing the suitability of hiPSC-CM platforms to evaluate contractility. We review issues, including maturity versus complexity, consistency, quality, and cost, while considering a potential need to incorporate auxiliary approaches to compensate for limitations in hiPSC-CM technology. We give examples on how coupling hiPSC-CM technologies with Cas9/CRISPR genome engineering is starting to be used to personalize diagnosis, stratify risk, provide mechanistic insights, and identify new pathogenic variants for cardiovascular disease.

Original languageEnglish
Pages (from-to)529-551
Number of pages23
JournalAnnual Review of Pharmacology and Toxicology
Volume60
DOIs
Publication statusPublished - 6 Jan 2020

Keywords

  • cardiac safety
  • cardiomyocyte contraction
  • Cas9/CRISPR
  • CiPA
  • human induced pluripotent stem cell-derived cardiomyocytes
  • organ-on-a-chip

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