High-throughput contractility analysis platform for drug-response evaluation of hiPSC-derived cardiac models based on...

Area of Science:

• Cardiovascular Research
• Pharmacology
• Stem Cell Biology

Background:

• Human pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are promising for in vitro drug testing.
• Immature phenotypes and experimental variability limit the predictive capability of current hiPSC-CM models.
• Novel strategies are needed to improve the reliability and accuracy of these cardiac models.

Purpose of the Study:

• To develop and validate a novel measurement strategy for assessing hiPSC-CMs in a dynamic frequency regime.
• To induce and analyze multiple contraction operation modes for improved drug evaluation.
• To enhance the predictive power of in vitro cardiac models for drug safety and efficacy.

Main Methods:

• Designed and validated a system for automated analysis of cardiac models using optical time-lapse microscopy in a dynamic regime.
• Employed repeated video-based measurements with physical conditioning, normalization, and adjustment.
• Investigated four benchmark models: 2D, 2DA, 3D-MTs, and EHTs in triple co-culture.

Main Results:

• The proposed strategy allows accurate estimation of drug responses through normalized video-based measurements.
• Analyzed operation modes increased the representativeness of contractile parameters and provided reliable concentration-response trends.
• The approach reduced the need for a high number of biological replicates.

Conclusions:

• The novel dynamic frequency measurement strategy is effective for evaluating drug responses in various hiPSC-CM models.
• This approach offers a promising foundation for developing high-throughput and robust pharmacological screening tools.
• The method improves the reliability of drug safety and efficacy evaluations using in vitro cardiac models.