Lemme, M. et al. (2018) Atrial-like engineered heart tissue: an in vitro model of the human atrium. Stem Cell Reports, 11(6), pp. 1378-1390. (doi: 10.1016/j.stemcr.2018.10.008) (PMID:30416051) (PMCID:PMC6294072)
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Abstract
Cardiomyocytes (CMs) generated from human induced pluripotent stem cells (hiPSCs) are under investigation for their suitability as human models in preclinical drug development. Antiarrhythmic drug development focuses on atrial biology for the treatment of atrial fibrillation. Here we used recent retinoic acid-based protocols to generate atrial CMs from hiPSCs and establish right atrial engineered heart tissue (RA-EHT) as a 3D model of human atrium. EHT from standard protocol-derived hiPSC-CMs (Ctrl-EHT) and intact human muscle strips served as comparators. RA-EHT exhibited higher mRNA and protein concentrations of atrial-selective markers, faster contraction kinetics, lower force generation, shorter action potential duration, and higher repolarization fraction than Ctrl-EHTs. In addition, RA-EHTs but not Ctrl-EHTs responded to pharmacological manipulation of atrial-selective potassium currents. RA- and Ctrl-EHTs’ behavior reflected differences between human atrial and ventricular muscle preparations. Taken together, RA-EHT is a model of human atrium that may be useful in preclinical drug screening.
| Item Type: | Articles |
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| Additional Information: | The work was supported by the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 675351, the German Ministry of Education and Research (BMBF) and German Centre for Cardiovascular Research (DZHK 81Z0710101), the European Research Council (ERC AG IndivuHeart), the Deutsche Forschungsgemeinschaft (DFG, HA 3423-5-1), and Leducq Fondation (research grant Nr. 11, CVD04). |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Smith, Professor Godfrey and Rol Garcia, Miriam |
| Authors: | Lemme, M., Ulmer, B. M., Lemoine, M. D., Zech, A. T.L., Flenner, F., Ravens, U., Reichenspurner, H., Rol-Garcia, M., Smith, G., Hansen, A., Christ, T., and Eschenhagen, T. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health |
| Journal Name: | Stem Cell Reports |
| Publisher: | Elsevier |
| ISSN: | 2213-6711 |
| ISSN (Online): | 2213-6711 |
| Published Online: | 08 November 2018 |
| Copyright Holders: | Copyright © 2018 The Authors |
| First Published: | First published in Stem Cell Reports 11(6):1378-1390 |
| Publisher Policy: | Reproduced under a Creative Commons license |
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