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Automated Contraction Analysis of Human Engineered Heart Tissue for Cardiac Drug Safety Screening
Published on: April 15, 2017
Human engineered heart tissue as a versatile tool in basic research and preclinical toxicology
Sebastian Schaaf1, Aya Shibamiya, Marco Mewe
1Department of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Plos One
|October 27, 2011
Summary
Researchers developed a human engineered heart tissue (hEHT) model using human embryonic stem cells (hESCs). This robust in vitro model enables functional studies of cardiomyocytes for heart research and drug testing.
Area of Science:
- Cardiovascular Research
- Stem Cell Biology
- Biomedical Engineering
Background:
- Human embryonic stem cells (hESCs) offer potential as substitutes for primary human cells, especially cardiomyocytes.
- Existing high-content experimental platforms for studying hESC-derived cardiomyocyte function under physiological conditions are limited.
Purpose of the Study:
- To establish a simple and robust protocol for generating human engineered heart tissue (hEHT) in a 24-well format.
- To validate hEHT as a functional in vitro model for cardiac research and drug screening.
Main Methods:
- Generation of fibrin-based hEHT using an unselected population of differentiated hESCs (30-40% α-actinin-positive cardiac myocytes).
- Automated video-optical recording for analyzing spontaneous hEHT contractions and responses to stimuli.
- Assessment of proarrhythmic compound effects on hEHT function.
Main Results:
- hEHTs exhibited coherent contractions within 5-10 days, maintaining regular and strong contractions for up to 8 weeks.
- Developed tissues showed organized, cross-striated cardiomyocyte networks.
- hEHTs demonstrated physiological responses to calcium, isoprenaline, and proarrhythmic drugs, correlating with hERG channel assay findings.
Conclusions:
- Human engineered heart tissue (hEHT) provides a simple and effective in vitro model for studying heart tissue function.
- This model is suitable for physiological and standardized research, including drug efficacy and toxicity testing.
