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Updated: Aug 11, 2025
Fabrication of 3D Cardiac Microtissue Arrays using Human iPSC-Derived Cardiomyocytes, Cardiac Fibroblasts, and Endothelial Cells
Published on: March 14, 2021
Action potential metrics and automated data analysis pipeline for cardiotoxicity testing using optically mapped
Arvin H Soepriatna1, Allison Navarrete-Welton2, Tae Yun Kim2
1Center for Biomedical Engineering, School of Engineering, Brown University, Providence, Rhode Island, United States of America.
This study introduces automated algorithms for analyzing human induced pluripotent stem cell-derived cardiac microtissues to assess drug cardiotoxicity. The new method enhances efficiency and accuracy in evaluating electrophysiological changes for compound safety testing.
Area of Science:
- Biomedical Engineering
- Stem Cell Biology
- Cardiovascular Research
Background:
- Human induced pluripotent stem cells (hiPSCs) enable the generation of cardiac microtissues for drug safety testing.
- Assessing cardiotoxicity of pharmaceutical and environmental compounds is crucial for drug development.
- Existing methods for cardiotoxicity assessment can be time-consuming and lack throughput.
Purpose of the Study:
- To develop automated data processing algorithms for analyzing action potential (AP) properties in 3D engineered cardiac microtissues.
- To establish a high-throughput in vitro platform for cardiotoxicity testing using hiPSC-derived cardiomyocytes (hiPSC-CMs).
- To validate the automated analysis pipeline using selective ion channel blockers.
Main Methods:
- Generated 3D cardiac microtissues by combining hiPSC-CMs and human cardiac fibroblasts (hCFs) under scaffold-free conditions.
- Utilized optical mapping with voltage-sensitive dye and CMOS camera for simultaneous AP acquisition from multiple microtissues.
- Developed automated algorithms for microtissue identification, background correction, signal normalization, and AP metric extraction (e.g., APD30, APD50, APD80).
Main Results:
- Successfully identified and analyzed AP traces from multiple cardiac microtissues simultaneously.
- Implemented automated data processing steps including background correction and signal normalization (ΔF/F0).
- Characterized AP shape changes and validated findings with computer simulations and pharmacological ion channel blockers.
Conclusions:
- The developed automated data analysis pipeline is simple, robust, and efficient for evaluating key AP metrics.
- This platform provides an excellent in vitro model for cardiotoxicity testing of diverse pharmaceutical and environmental compounds.
- The study demonstrates the utility of hiPSC-derived cardiac microtissues for predictive toxicology in drug development.
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