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

  • Author(s): Feyen, Dries AM
  • McKeithan, Wesley L
  • Bruyneel, Arne AN
  • Spiering, Sean
  • Hörmann, Larissa
  • Ulmer, Bärbel
  • Zhang, Hui
  • Briganti, Francesca
  • Schweizer, Michaela
  • Hegyi, Bence
  • Liao, Zhandi
  • Pölönen, Risto-Pekka
  • Ginsburg, Kenneth S
  • Lam, Chi Keung
  • Serrano, Ricardo
  • Wahlquist, Christine
  • Kreymerman, Alexander
  • Vu, Michelle
  • Amatya, Prashila L
  • Behrens, Charlotta S
  • Ranjbarvaziri, Sara
  • Maas, Renee GC
  • Greenhaw, Matthew
  • Bernstein, Daniel
  • Wu, Joseph C
  • Bers, Donald M
  • Eschenhagen, Thomas
  • Metallo, Christian M
  • Mercola, Mark
  • et al.
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.

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