human engineered heart tissue: analysis of contractile force
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ID: 170777
2016
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Abstract
Analyzing contractile force, the most important and best understood function of cardiomyocytes in vivo is not established in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM). This study describes the generation of 3D, strip-format, force-generating engineered heart tissues (EHT) from hiPSC-CM and their physiological and pharmacological properties. CM were differentiated from hiPSC by a growth factor-based three-stage protocol. EHTs were generated and analyzed histologically and functionally. HiPSC-CM in EHTs showed well-developed sarcomeric organization and alignment, and frequent mitochondria. Systematic contractility analysis (26 concentration-response curves) reveals that EHTs replicated canonical response to physiological and pharmacological regulators of inotropy, membrane- and calcium-clock mediators of pacemaking, modulators of ion-channel currents, and proarrhythmic compounds with unprecedented precision. The analysis demonstrates a high degree of similarity between hiPSC-CM in EHT format and native human heart tissue, indicating that human EHTs are useful for preclinical drug testing and disease modeling.
| Reference Key |
mannhardt2016stemhuman
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| Authors | ;Ingra Mannhardt;Kaja Breckwoldt;David Letuffe-Brenière;Sebastian Schaaf;Herbert Schulz;Christiane Neuber;Anika Benzin;Tessa Werner;Alexandra Eder;Thomas Schulze;Birgit Klampe;Torsten Christ;Marc N. Hirt;Norbert Huebner;Alessandra Moretti;Thomas Eschenhagen;Arne Hansen |
| Journal | nature reviews gastroenterology & hepatology |
| Year | 2016 |
| DOI |
10.1016/j.stemcr.2016.04.011
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| URL | |
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