Human iPSC-engineered cardiac tissue platform faithfully models important cardiac physiology

Area of Science:

• Biomedical Engineering
• Cardiovascular Research
• Stem Cell Biology

Background:

• Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are promising for disease modeling but immature.
• Traditional 2D cultures lack key features of adult myocardium, limiting physiological relevance.
• Maturation of hiPSC-CMs is crucial for accurate preclinical drug screening and disease studies.

Purpose of the Study:

• To assess a novel 3D co-culture system of hiPSC-CMs and cardiac fibroblasts in a fibrin matrix (hiPSC-ECTs).
• To evaluate the maturation and physiological responsiveness of hiPSC-ECTs compared to human myocardium and other engineered tissues.
• To provide data aiding the selection of appropriate engineered cardiac tissue platforms for research.

Main Methods:

• Co-culture of hiPSC-CMs and hiPSC-derived cardiac fibroblasts in a 3D fibrin matrix to form engineered cardiac tissue constructs (hiPSC-ECTs).
• Assessment of hiPSC-ECTs' responsiveness to physiological stimuli (stretch, frequency, β-adrenergic stimulation).
• Analysis of t-tubular system development, intracellular calcium handling, contractile kinetics, and gene expression related to maturation.

Main Results:

• hiPSC-ECTs developed a t-tubular system and exhibited improved calcium handling and contractile kinetics compared to 2D cultures.
• Constructs responded physiologically to stretch, frequency, and β-adrenergic stimulation.
• Markers of cardiac maturation, including gene transcript levels, increased robustly over 6 weeks in culture.

Conclusions:

• The 3D co-culture system effectively promotes maturation of hiPSC-CMs, creating a physiologically relevant engineered cardiac tissue.
• hiPSC-ECTs offer a valuable human cardiac model for research, requiring only standard equipment and no additional stimuli.
• This platform provides detailed physiological data and aids in selecting the best engineered tissue model for specific research applications.