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

Bärbel M Ulmer1, Andrea Stoehr2, Mirja L Schulze1

  • 1University 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.

Stem Cell Reports
|March 6, 2018
PubMed

Insights

Cultivating human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in 3D engineered heart tissue promotes metabolic maturation. Contractile work is crucial for this enhanced energy metabolism in hiPSC-CMs.

Area of Science:

  • Cardiology
  • Stem Cell Biology
  • Metabolic Research

Background:

  • Cardiomyocyte energy metabolism is vital for heart function.
  • Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are immature and lack postnatal metabolic development.
  • Biomedical applications require metabolically mature cardiomyocytes.

Purpose of the Study:

  • To determine if 3D engineered heart tissue culture matures hiPSC-CM energy metabolism compared to 2D culture.
  • To investigate the role of contractile work in hiPSC-CM metabolic maturation.

Main Methods:

  • Comparison of mitochondrial and metabolic states in 3D vs. 2D hiPSC-CM cultures.
  • Analysis of mitochondrial mass, DNA content, and proteome.
  • Assessment of substrate utilization (glucose, lactate, fatty acids) and glycolysis.
  • Pharmacological inhibition of contractile force to evaluate its impact.

Main Results:

  • 3D hiPSC-CMs exhibited increased mitochondrial mass, DNA, and proteome compared to 2D cultures.
  • hiPSC-CMs utilized glucose, lactate, and fatty acids in both formats.
  • 3D culture enhanced substrate oxidation and reduced anaerobic glycolysis.
  • Reduced contractile force diminished the increase in mitochondrial mass and DNA in 3D cultures.

Conclusions:

  • 3D engineered heart tissue promotes metabolic maturation of hiPSC-CMs.
  • Contractile activity is a key driver of metabolic development in hiPSC-CMs.
  • This finding has implications for developing more mature hiPSC-CMs for research and therapy.

Keywords:
developmental hypertrophyengineered heart tissuehuman induced pluripotent stem cell-derived cardiomyocytesmaturationmetabolism

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