Details

Autor(en) / Beteiligte

• 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

Titel

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

Ist Teil von

• Cell reports (Cambridge), 2020-07, Vol.32 (3), p.107925-107925, Article 107925

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2020

Quelle

Electronic Journals Library

Beschreibungen/Notizen

• 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. [Display omitted] •We developed a defined maturation medium for hiPSC-CMs•The media improve electrophysiological and mechanical characteristics of hiPSC-CMs•The media improve the fidelity of disease modeling Physiological immaturity of iPSC-derived cardiomyocytes limits their fidelity as disease models. Feyen et al. developed a low glucose, high oxidative substrate media that increase maturation of ventricular-like hiPSC-CMs in 2D and 3D cultures relative to standard protocols. Improved characteristics include a low resting Vm, rapid depolarization, and increased Ca2+ dependence and force generation.