Functional arrays of human pluripotent stem cell-derived cardiac microtissues

Area of Science:

• Biomedical Engineering
• Stem Cell Biology
• Cardiovascular Research

Background:

• Accelerating cardiac drug discovery requires robust platforms for quantifying tissue-level function.
• Existing methods often lack the throughput or sensitivity needed for comprehensive screening.
• Human pluripotent stem cell (hPSC)-derived cardiac tissues offer a promising model for disease and drug testing.

Purpose of the Study:

• To develop a 96-well platform for measuring contractile force of 3D cardiac microtissues.
• To create an open-source system amenable to standard multiwell-plate manipulations for drug screening.
• To enable high-throughput analysis of cardiac tissue function using human pluripotent stem cell-derived models.

Main Methods:

• Fabrication of 3D-printed multiwell plates with elastomeric microcantilevers and circumferential ramps.
• Self-organization of hPSC-derived cardiac microtissues (CaMiRi) around microcantilevers within wells.
• Measurement of contractile force via microcantilever deflection and validation with cardiotropic compounds.

Main Results:

• Demonstrated robust and reproducible contractile force measurements across wells.
• Optimized tissue formulation and validated CaMiRi response with known drugs.
• Developed automated protocols for seeding, imaging, and analysis, increasing throughput.

Conclusions:

• The CaMiRi platform provides an open-source, high-throughput system for cardiac contractile force screening.
• This technology can significantly accelerate cardiac drug discovery and advance tissue engineering applications.
• Integration of hPSC-derived epicardial cells highlights the platform's versatility in studying complex cardiac tissue interactions.