Miniaturized engineered heart tissues from hiPSC-derived triple cell type co-cultures to study human cardiac function

Area of Science:

• Cardiovascular Biology
• Stem Cell Technology
• Biomedical Engineering

Background:

• Three-dimensional human heart tissues from pluripotent stem cells model physiology better than 2D models.
• Standard engineered heart tissues (EHTs) require millions of cells, limiting large-scale screening due to cost.
• Existing models like spheroids lack the ability to measure contraction force.

Purpose of the Study:

• To create a physiologically relevant, miniaturized EHT model using fewer cells.
• To ensure the miniaturized EHT model retains correct cardiac functionality.
• To reduce the cost of EHTs for widespread use in research and drug discovery.

Main Methods:

• Generated EHTs using a combination of human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (70%), cardiac fibroblasts (15%), and cardiac endothelial cells (15%).
• Utilized a downscaled EHT design requiring as few as 1.6 × 10^4 cells.
• Assessed EHT viability, functionality, and response to electrical pacing up to 14 days post-formation.

Main Results:

• Fully functional miniaturized EHTs were successfully generated with a significantly reduced cell count.
• The EHTs demonstrated viability and consistent functionality for up to 14 days.
• Miniaturized EHTs responded to electrical pacing in a physiologically relevant frequency range (0.6–3 Hz).

Conclusions:

• Miniaturized EHTs represent a viable and functional microphysiological system.
• This downscaled model offers a cost-effective alternative to conventional EHTs for disease modeling.
• These findings support the use of miniaturized EHTs in drug discovery, particularly for secondary screening.