Automated image analysis system for studying cardiotoxicity in human pluripotent stem cell-Derived cardiomyocytes
Related Experiment Video
Updated: Dec 21, 2025
High-Throughput Cardiotoxicity Screening Using Mature Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Monolayers
Published on: March 24, 2023
Lu Cao1, Andries D van der Meer2, Fons J Verbeek3
1Imaging and Bioinformatics group, Leiden Institute of Advanced Computer Science (LIACS), Leiden University, Niels Bohrweg 1, Leiden, 2333 CA, The Netherlands.
Background:
Cardiotoxicity, characterized by severe cardiac dysfunction, is a major problem in patients treated with different classes of anticancer drugs. Development of predictable human-based models and assays for drug screening are crucial for preventing potential drug-induced adverse effects. Current animal in vivo models and cell lines are not always adequate to represent human biology. Alternatively, human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) show great potential for disease modelling and drug-induced toxicity screenings. Fully automated high-throughput screening of drug toxicity on hiPSC-CMs by fluorescence image analysis is, however, very challenging, due to clustered cell growth patterns and strong intracellular and intercellular variation in the expression of fluorescent markers.
Results:
In this paper, we report on the development of a fully automated image analysis system for quantification of cardiotoxic phenotypes from hiPSC-CMs that are treated with various concentrations of anticancer drugs doxorubicin or crizotinib. This high-throughput system relies on single-cell segmentation by nuclear signal extraction, fuzzy C-mean clustering of cardiac α-actinin signal, and finally nuclear signal propagation. When compared to manual segmentation, it generates precision and recall scores of 0.81 and 0.93, respectively.
Conclusions:
Our results show that our fully automated image analysis system can reliably segment cardiomyocytes even with heterogeneous α-actinin signals.
Insights
This study presents an automated image analysis system to reliably detect drug-induced cardiotoxicity in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). The system accurately quantifies toxic effects, improving drug screening for safer anticancer therapies.
Area of Science:
- Biomedical Engineering
- Cardiovascular Research
- Drug Discovery
Background:
- Anticancer drugs can cause cardiotoxicity, leading to severe cardiac dysfunction.
- Current drug screening models (animal, cell lines) inadequately represent human biology.
- Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) offer a promising human-based model for toxicity screening.
Purpose of the Study:
- To develop a fully automated image analysis system for high-throughput drug toxicity screening on hiPSC-CMs.
- To overcome challenges in automated analysis caused by clustered cell growth and variable fluorescent marker expression.
- To enable reliable quantification of cardiotoxic phenotypes induced by anticancer drugs.
Main Methods:
- Developed a high-throughput system for automated image analysis of hiPSC-CMs.
- Employed single-cell segmentation via nuclear signal extraction.
- Utilized fuzzy C-mean clustering for cardiac α-actinin signal and nuclear signal propagation.
Main Results:
- The automated system accurately quantifies cardiotoxic phenotypes from hiPSC-CMs treated with doxorubicin or crizotinib.
- Achieved high precision (0.81) and recall (0.93) scores compared to manual segmentation.
- Demonstrated reliable segmentation of cardiomyocytes despite heterogeneous α-actinin signals.
Conclusions:
- The developed automated image analysis system reliably segments cardiomyocytes.
- This system enables accurate quantification of drug-induced cardiotoxicity in hiPSC-CMs.
- The technology facilitates improved drug screening for safer anticancer treatments.
More Related Videos
08:03Hybrid Cell Analysis System to Assess Structural and Contractile Changes of Human iPSC-Derived Cardiomyocytes for Preclinical Cardiac Risk Evaluation
Published on: October 20, 2022
10:30Technical Applications of Microelectrode Array and Patch Clamp Recordings on Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes
Published on: August 4, 2022