期刊
CELL REPORTS
卷 32, 期 3, 页码 -出版社
CELL PRESS
DOI: 10.1016/j.celrep.2020.107925
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资金
- NIH [R01HL113006, R01HL130840, R01HL128072, R21HL141019, R01HL132225, P01HL141084]
- Foundation Leducq (CurePLaN)
- AHA [18CDA34070040]
- CIRM [RB5-07356]
- European Union [708459]
- Marie Curie Actions (MSCA) [708459] Funding Source: Marie Curie Actions (MSCA)
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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