Metabolic Maturation Media Improve Physiological Function of Human iPSC-Derived Cardiomyocytes
Summary
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. Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
| Authors | Feyen DAM, McKeithan WL, Bruyneel AAN, Spiering S, Hörmann L, Ulmer B, Zhang H, Briganti F, Schweizer M, Hegyi B, Liao Z, Pölönen RP, Ginsburg KS, Lam CK, Serrano R, Wahlquist C, Kreymerman A, Vu M, Amatya PL, Behrens CS, Ranjbarvaziri S, Maas RGC, Greenhaw M, Bernstein D, Wu JC, Bers DM, Eschenhagen T, Metallo CM, Mercola M |
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| Journal | Cell reports |
| Publication Date | 2020 Jul 21;32(3):107925 |
| PubMed | 32697997 |
| PubMed Central | PMC7437654 |
| DOI | 10.1016/j.celrep.2020.107925 |