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Automated Contraction Analysis of Human Engineered Heart Tissue for Cardiac Drug Safety Screening
Published on: April 15, 2017
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Human Engineered Heart Tissue: Analysis of Contractile Force
Ingra Mannhardt1, Kaja Breckwoldt1, David Letuffe-Brenière1
1Department of Experimental Pharmacology and Toxicology, Cardiovascular Research Center, University Medical Center Hamburg-Eppendorf, DZHK (German Center for Cardiovascular Research), Partner Site Hamburg/Kiel/Lübeck, 20246 Hamburg, Germany.
Stem Cell Reports
|May 24, 2016
Summary
Human engineered heart tissues (EHTs) from stem cells accurately mimic native heart muscle function. This breakthrough enables precise preclinical drug testing and disease modeling for cardiovascular research.
Area of Science:
- Cardiovascular Research
- Stem Cell Biology
- Biomedical Engineering
Background:
- Contractile function of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) in vivo remains incompletely understood.
- Accurate functional assessment of hiPSC-CM is crucial for preclinical drug testing and disease modeling.
Purpose of the Study:
- To generate 3D, force-generating engineered heart tissues (EHTs) from hiPSC-CM.
- To characterize the physiological and pharmacological properties of these hiPSC-CM-derived EHTs.
- To establish a reliable model for studying human cardiomyocyte function and drug responses.
Main Methods:
- Differentiation of cardiomyocytes from hiPSC using a three-stage growth factor protocol.
- Generation of 3D strip-format engineered heart tissues (EHTs).
- Histological and functional analysis, including systematic contractility assessment (26 concentration-response curves).
Main Results:
- hiPSC-CM within EHTs exhibited well-developed sarcomeric organization, alignment, and abundant mitochondria.
- EHTs precisely replicated canonical responses to physiological regulators, inotropic agents, pacemaking mediators, ion channel modulators, and proarrhythmic compounds.
- Demonstrated high similarity in contractile function between hiPSC-CM in EHT format and native human heart tissue.
Conclusions:
- Human engineered heart tissues (EHTs) provide a robust platform for functional analysis of hiPSC-CM.
- EHTs accurately model human cardiomyocyte physiology and pharmacology.
- This model is highly valuable for preclinical drug efficacy and safety testing, as well as cardiovascular disease modeling.
