Metabolic Maturation Media Improve Physiological Function of Human iPSC-Derived Cardiomyocytes
Feyen, Dries A M; McKeithan, Wesley L; Bruyneel, Arne A N; 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 G C; Greenhaw, Matthew; Bernstein, Daniel; Wu, Joseph C; Bers, Donald M; Eschenhagen, Thomas; Metallo, Christian M; Mercola, Mark
(2020) Cell Reports, volume 32, issue 3
(Article)
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
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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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Keywords: cardiomyocyte, dilated cardiomyopathy, disease modeling, engineered heart tissues, induced pluripotent stem cells, long QT syndrome 3, maturation, physiology, General Biochemistry,Genetics and Molecular Biology
ISSN: 2211-1247
Publisher: Cell Press
Note: Publisher Copyright: © 2020 The Authors
(Peer reviewed)