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 journal › SCORING: Journal article › Research › peer-review
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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 -