Human-induced pluripotent stem cell-derived cardiomyocytes exhibit temporal changes in phenotype

Area of Science:

• Cardiovascular Research
• Stem Cell Biology
• Pharmacology

Background:

• Human-induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) are valuable tools for research.
• However, their functional maturity and optimal use are debated due to variable phenotypes.

Purpose of the Study:

• To characterize the temporal maturation of hiPS-CM phenotype.
• To assess key determinants of cardiomyocyte function over time in culture.

Main Methods:

• Examined gene expression, ion channel function, calcium cycling, metabolic activity, and drug responses.
• Utilized electrophysiology, gene expression analysis, and pharmacological profiling.
• Investigated effects of thyroid hormone treatment on hiPS-CM maturation.

Main Results:

• hiPS-CMs show progressive maturation from day 30 without dedifferentiation.
• Mature hiPS-CMs exhibit adult-like gene expression, electrophysiology, and calcium handling.
• They respond to cardioactive compounds similarly to adult cardiomyocytes.
• Thyroid hormone treatment promoted a more adult-like gene expression pattern.

Conclusions:

• hiPS-CMs acquire progressive functionality with extended culture time.
• Understanding this evolving phenotype is crucial for optimizing hiPS-CM applications in research and drug testing.
• hiPS-CMs represent a dynamic model for studying cardiomyocyte development and function.