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

Cell Reports
Dries A M FeyenMark Mercola

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 (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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Citations

Oct 22, 2020·International Journal of Molecular Sciences·Lin JiangYigang Wang
Feb 13, 2021·International Journal of Molecular Sciences·María Julia BarisónBruno Dallagiovanna
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Datasets Mentioned

BETA
GSE151279

Methods Mentioned

BETA
flow cytometry
RNA-seq
transfection
PCR
Assay
biopsies
electron

Software Mentioned

Rsubread
pClamp10
DESeq2 Bioconductor
GraphPad Prism
Zeiss Zen
trimmomatic
STAR
FastQC
ImageJ
NIS Elements AR

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