Human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) are a widely used platform in cardiac research. They offer a patient-specific model for investigating disease mechanisms, cardiotoxicity, and drug responses. However, their structural and functional immaturity remains a significant limitation, particularly for applications requiring adult-like electrophysiological behavior.

A recent study by Wener Li and colleagues (Technische Universität Dresden) explored how combining metabolic, structural, and electrical treatments could promote iPSC-CM maturation over a 42-day protocol:

• Metabolic maturation medium (MM): Supplemented with fatty acids and higher calcium.
• Nanopatterning (NP): Used to promote cell alignment.
• Electrostimulation (ES): Applied at 2 Hz to mimic physiological heart rhythms.

What did they observe?

• Improved structural organization with aligned sarcomeres and enhanced Cx43 membrane localization in the MM+NP+ES condition.
• Mature electrophysiological signatures, including “notch-and-dome” action potentials, hyperpolarized resting membrane potential, and increased upstroke velocity.
• Enhanced drug response, with more predictable effects of verapamil and E-4031 compared to immature iPSC-CMs.
• Transcriptomic insights suggesting mitochondrial activation (via TFAM, HMCES) and downregulation of MAPK/PI3K-AKT pathways linked to polyploidy and differentiation.

To assess ion channel function, selected current measurements (I_Na, I_K1, I_to, I_Ca-L) were obtained using automated patch clamp (Patchliner). This approach provided reproducible single-cell data across different maturation conditions, supporting the interpretation of functional outcomes.

This study highlights the benefits of combining metabolic, structural, and electrical signal to help iPSC-CMs behave more like adult heart cells. The findings are especially relevant for improving drug testing and disease modeling.

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🔗 Read the full article:
Comprehensive promotion of iPSC-CM maturation by integrating metabolic medium with nanopatterning and electrostimulation

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https://www.nanion.de/product-categories/automated-patch-clamp/