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Updated: Apr 7, 2026
Fabrication of 3D Cardiac Microtissue Arrays using Human iPSC-Derived Cardiomyocytes, Cardiac Fibroblasts, and Endothelial Cells
Published on: March 14, 2021
Stem cell derived in vivo-like human cardiac bodies in a microfluidic device for toxicity testing by beating
Gunnar Bergström1, Jonas Christoffersson, Kristin Schwanke
1Division of Biotechnology, Dept. of Physics, Chemistry and Biology (IFM), Linköping University, 58183 Linköping, Sweden. cfm@ifm.liu.se.
Insights
This study introduces a novel microfluidic device using beating human cardiac bodies (CBs) for drug cardiotoxicity testing. The system enables label-free, non-invasive assessment of toxic effects on 3D cardiomyocyte cultures.
Area of Science:
- Biomedical Engineering
- Cardiovascular Research
- Toxicology
Background:
- Developing reliable in vitro models for human cardiac toxicity testing is crucial for drug development.
- Induced pluripotent stem cell-derived cardiomyocytes offer a promising source for patient-specific cardiac models.
- Existing methods for assessing cardiotoxicity can be invasive or lack 3D structural relevance.
Purpose of the Study:
- To develop and validate a microfluidic device for assessing cardiotoxicity using beating human cardiac bodies (CBs).
- To evaluate the efficacy of the system in detecting known cardiotoxic drug effects.
- To establish a label-free, non-invasive method for monitoring cardiomyocyte function in a 3D microenvironment.
Main Methods:
- Generation of in vivo-like human cardiac bodies (CBs) from induced pluripotent stem cells.
- Integration of CBs into a microfluidic device with specialized niches for perfusion.
- Automated video imaging for real-time monitoring of individual CB beating frequency.
- Exposure of CBs to known cardiotoxic drugs (doxorubicin, verapamil, quinidine) and analysis of beating frequency changes.
Main Results:
- The microfluidic device successfully maintained and monitored beating human cardiac bodies.
- Significant changes in beating frequency were observed in response to doxorubicin, verapamil, and quinidine.
- The results demonstrated the system's sensitivity in detecting drug-induced cardiotoxicity.
- Collected data over 6 hours showed good correlation with literature values.
Conclusions:
- The developed microfluidic platform with human cardiac bodies provides a robust model for cardiotoxicity screening.
- This label-free, non-invasive imaging approach offers a valuable tool for preclinical drug safety assessment.
- The 3D microenvironment in the device better mimics native cardiac tissue, enhancing predictive power.
Abstract:
Beating in vivo-like human cardiac bodies (CBs) were used in a microfluidic device for testing cardiotoxicity. The CBs, cardiomyocyte cell clusters derived from induced pluripotent stem cells, exhibited typical structural and functional properties of the native human myocardium. The CBs were captured in niches along a perfusion channel in the device. Video imaging was utilized for automatic monitoring of the beating frequency of each individual CB. The device allowed assessment of cardiotoxic effects of drug substances doxorubicin, verapamil and quinidine on the 3D clustered cardiomyocytes. Beating frequency data recorded over a period of 6 hours are presented and compared to literature data. The results indicate that this microfluidic setup with imaging of CB characteristics provides a new opportunity for label-free, non-invasive investigation of toxic effects in a 3D microenvironment.
