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Stem Cell Reports. 2018 Mar 13;10(3):834-847. doi: 10.1016/j.stemcr.2018.01.039. Epub 2018 Mar 1.

Contractile Work Contributes to Maturation of Energy Metabolism in hiPSC-Derived Cardiomyocytes.

Author information

1
University Medical Center Hamburg Eppendorf, Department of Experimental Pharmacology and Toxicology, 20246 Hamburg, Germany; German Center for Heart Research (DZHK), Partner Site Hamburg/Kiel/Lübeck, Hamburg, Germany. Electronic address: b.ulmer@uke.de.
2
Systems Biology Center, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
3
University Medical Center Hamburg Eppendorf, Department of Experimental Pharmacology and Toxicology, 20246 Hamburg, Germany; German Center for Heart Research (DZHK), Partner Site Hamburg/Kiel/Lübeck, Hamburg, Germany.
4
Proteomics Core Facility, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
5
University Medical Center Hamburg Eppendorf, Department of Experimental Pharmacology and Toxicology, 20246 Hamburg, Germany; German Center for Heart Research (DZHK), Partner Site Hamburg/Kiel/Lübeck, Hamburg, Germany. Electronic address: ar.hansen@uke.de.

Abstract

Energy metabolism is a key aspect of cardiomyocyte biology. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are a promising tool for biomedical application, but they are immature and have not undergone metabolic maturation related to early postnatal development. To assess whether cultivation of hiPSC-CMs in 3D engineered heart tissue format leads to maturation of energy metabolism, we analyzed the mitochondrial and metabolic state of 3D hiPSC-CMs and compared it with 2D culture. 3D hiPSC-CMs showed increased mitochondrial mass, DNA content, and protein abundance (proteome). While hiPSC-CMs exhibited the principal ability to use glucose, lactate, and fatty acids as energy substrates irrespective of culture format, hiPSC-CMs in 3D performed more oxidation of glucose, lactate, and fatty acid and less anaerobic glycolysis. The increase in mitochondrial mass and DNA in 3D was diminished by pharmacological reduction of contractile force. In conclusion, contractile work contributes to metabolic maturation of hiPSC-CMs.

KEYWORDS:

developmental hypertrophy; engineered heart tissue; human induced pluripotent stem cell-derived cardiomyocytes; maturation; metabolism

PMID:
29503093
PMCID:
PMC5919410
DOI:
10.1016/j.stemcr.2018.01.039
[Indexed for MEDLINE]
Free PMC Article

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