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

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Contractile Work Contributes to Maturation of Energy Metabolism in hiPSC-Derived Cardiomyocytes. / Ulmer, Bärbel M; Stoehr, Andrea; Schulze, Mirja L; Patel, Sajni; Gucek, Marjan; Mannhardt, Ingra; Funcke, Sandra; Murphy, Elizabeth; Eschenhagen, Thomas; Hansen, Arne.

In: STEM CELL REP, Vol. 10, No. 3, 13.03.2018, p. 834-847.

Research output: SCORING: Contribution to journalSCORING: Journal articleResearchpeer-review

Harvard

Ulmer, BM, Stoehr, A, Schulze, ML, Patel, S, Gucek, M, Mannhardt, I, Funcke, S, Murphy, E, Eschenhagen, T & Hansen, A 2018, 'Contractile Work Contributes to Maturation of Energy Metabolism in hiPSC-Derived Cardiomyocytes', STEM CELL REP, vol. 10, no. 3, pp. 834-847. https://doi.org/10.1016/j.stemcr.2018.01.039

APA

Ulmer, B. M., Stoehr, A., Schulze, M. L., Patel, S., Gucek, M., Mannhardt, I., Funcke, S., Murphy, E., Eschenhagen, T., & Hansen, A. (2018). Contractile Work Contributes to Maturation of Energy Metabolism in hiPSC-Derived Cardiomyocytes. STEM CELL REP, 10(3), 834-847. https://doi.org/10.1016/j.stemcr.2018.01.039

Vancouver

Bibtex

@article{021fcae4d33d4dfea9f3d2a6344da9d3,
title = "Contractile Work Contributes to Maturation of Energy Metabolism in hiPSC-Derived Cardiomyocytes",
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 = "Cell Differentiation, Cells, Cultured, Energy Metabolism, Fatty Acids, Glucose, Glycolysis, Humans, Induced Pluripotent Stem Cells, Lactic Acid, Mitochondria, Muscle Contraction, Myocytes, Cardiac, Journal Article, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't",
author = "Ulmer, {B{\"a}rbel M} and Andrea Stoehr and Schulze, {Mirja L} and Sajni Patel and Marjan Gucek and Ingra Mannhardt and Sandra Funcke and Elizabeth Murphy and Thomas Eschenhagen and Arne Hansen",
note = "Copyright {\textcopyright} 2018 The Author(s). Published by Elsevier Inc. All rights reserved.",
year = "2018",
month = mar,
day = "13",
doi = "10.1016/j.stemcr.2018.01.039",
language = "English",
volume = "10",
pages = "834--847",
journal = "STEM CELL REP",
issn = "2213-6711",
publisher = "Cell Press",
number = "3",

}

RIS

TY - JOUR

T1 - Contractile Work Contributes to Maturation of Energy Metabolism in hiPSC-Derived Cardiomyocytes

AU - Ulmer, Bärbel M

AU - Stoehr, Andrea

AU - Schulze, Mirja L

AU - Patel, Sajni

AU - Gucek, Marjan

AU - Mannhardt, Ingra

AU - Funcke, Sandra

AU - Murphy, Elizabeth

AU - Eschenhagen, Thomas

AU - Hansen, Arne

N1 - Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

PY - 2018/3/13

Y1 - 2018/3/13

N2 - 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.

AB - 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.

KW - Cell Differentiation

KW - Cells, Cultured

KW - Energy Metabolism

KW - Fatty Acids

KW - Glucose

KW - Glycolysis

KW - Humans

KW - Induced Pluripotent Stem Cells

KW - Lactic Acid

KW - Mitochondria

KW - Muscle Contraction

KW - Myocytes, Cardiac

KW - Journal Article

KW - Research Support, N.I.H., Intramural

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.stemcr.2018.01.039

DO - 10.1016/j.stemcr.2018.01.039

M3 - SCORING: Journal article

C2 - 29503093

VL - 10

SP - 834

EP - 847

JO - STEM CELL REP

JF - STEM CELL REP

SN - 2213-6711

IS - 3

ER -