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

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2020 Jul 23

PMID 32697997

Citations 167

Authors

Dries A M Feyen

Wesley L McKeithan

Arne A N Bruyneel

Sean Spiering

Larissa Hormann

Barbel Ulmer

Hui Zhang

Francesca Briganti

Michaela Schweizer

Bence Hegyi

Zhandi Liao

Risto-Pekka Polonen

Kenneth S Ginsburg

Chi Keung Lam

Ricardo Serrano

Christine Wahlquist

Alexander Kreymerman

Michelle Vu

Prashila L Amatya

Charlotta S Behrens

Sara Ranjbarvaziri

Renee G C Maas

Matthew Greenhaw

Daniel Bernstein

Joseph C Wu

Donald M Bers

Thomas Eschenhagen

Christian M Metallo

Mark Mercola

Affiliations

Soon will be listed here.

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 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) 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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