Metabolic Maturation Media Improve Physiological Function of Human iPSC-Derived Cardiomyocytes

Dries A.M. Feyen, Wesley L. McKeithan, Arne A.N. Bruyneel, Sean Spiering, Larissa Hörmann, Bärbel Ulmer, Hui Zhang, Francesca Briganti, Michaela Schweizer, Bence Hegyi, Zhandi Liao, Risto Pekka Pölönen, Kenneth S Ginsburg, Chi Keung Lam, Ricardo Serrano, Christine Wahlquist, Alexander Kreymerman, Michelle Vu, Prashila L. Amatya, Charlotta S. BehrensSara Ranjbarvaziri, Renee G.C. Maas, Matthew Greenhaw, Daniel Bernstein, Joseph C. Wu, Donald M. Bers, Thomas Eschenhagen, Christian M. Metallo, Mark Mercola

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) have enormous potential for the study of human cardiac disorders. However, their physiological immaturity severely limits their utility as a model system and their adoption for drug discovery. Here, we describe maturation media designed to provide oxidative substrates adapted to the metabolic needs of human iPSC (hiPSC)-CMs. Compared with conventionally cultured hiPSC-CMs, metabolically matured hiPSC-CMs contract with greater force and show an increased reliance on cardiac sodium (Na+) channels and sarcoplasmic reticulum calcium (Ca2+) cycling. The media enhance the function, long-term survival, and sarcomere structures in engineered heart tissues. Use of the maturation media made it possible to reliably model two genetic cardiac diseases: long QT syndrome type 3 due to a mutation in the cardiac Na+ channel SCN5A and dilated cardiomyopathy due to a mutation in the RNA splicing factor RBM20. The maturation media should increase the fidelity of hiPSC-CMs as disease models.

Original languageEnglish (US)
Article number107925
JournalCell Reports
Volume32
Issue number3
DOIs
StatePublished - Jul 21 2020

Keywords

  • cardiomyocyte
  • dilated cardiomyopathy
  • disease modeling
  • engineered heart tissues
  • induced pluripotent stem cells
  • long QT syndrome 3
  • maturation
  • physiology

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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