- 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
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.