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

作者：Dries 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 M. Vu, Prashila Amatya, Charlotta Sophie Behrens, Sara Ranjbarvaziri, Renée G. C. Maas, Matthew Greenhaw, Daniel Bernstein, Joseph C. Wu, Donald M. Bers, Thomas Eschenhagen, Christian M. Metallo, Mark Mercola · 发表于：Cell Reports · 年份：2020 · DOI：10.1016/j.celrep.2020.107925 · 被引用次数：410 · 研究领域：CRISPR and Genetic Engineering、Pluripotent Stem Cells Research、Neuroscience and Neural Engineering

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 (Ca 2+ ) 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.