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Formation of an electrical coupling between differentiating cardiomyocytes

M M Slotvitsky1, V A Tsvelaya1, A D Podgurskaya1

  • 1Moscow Institute of Physics and Technology, Dolgoprudny, Moscow Region, 141700, Russian Federation.

Scientific Reports
|May 10, 2020
PubMed

Insights

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) form functional syncytia for cardiovascular disease research. Early seeding (before day 20) ensures stable excitation wave conduction, unlike later seeding which causes instability.

Area of Science:

  • Cardiovascular Research
  • Stem Cell Biology
  • Electrophysiology

Background:

  • Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are vital for studying cardiovascular diseases.
  • Research has focused on individual cells, neglecting the syncytium's properties crucial for cardiac function.
  • Understanding syncytium formation is key to accurately modeling cardiac electrophysiology.

Purpose of the Study:

  • To investigate the ability of hiPSC-CMs to form a functional syncytium.
  • To assess the stable conduction of excitation waves within hiPSC-CM syncytia.
  • To determine the optimal differentiation stage for hiPSC-CM seeding to form a functional syncytium.

Main Methods:

  • hiPSC-CMs were harvested and re-seeded onto new substrates at various differentiation days.
  • Optical mapping was employed to characterize excitation conduction and wavefront stability.
  • Analysis focused on the homogeneity of syncytium formation and the stability of wave propagation.

Main Results:

  • hiPSC-CMs seeded before day 20 of differentiation formed functional syncytia.
  • These early-seeded syncytia demonstrated stable excitation conduction, even at high stimulation frequencies.
  • Cells seeded after day 20 failed to form homogeneous syncytia, exhibiting wavefront instabilities and potential reentry.

Conclusions:

  • The differentiation day of hiPSC-CMs significantly impacts their ability to form a functional syncytium.
  • Seeding hiPSC-CMs before day 20 is critical for establishing stable excitation wave conduction.
  • This finding is crucial for developing reliable hiPSC-CM models for cardiovascular research and drug testing.

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