Atrial-like Engineered Heart Tissue: An In Vitro Model of the Human Atrium
Summary: 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 r...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2018-12-01
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| Series: | Stem Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213671118304314 |
| _version_ | 1818788373623472128 |
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| author | Marta Lemme Bärbel M. Ulmer Marc D. Lemoine Antonia T.L. Zech Frederik Flenner Ursula Ravens Hermann Reichenspurner Miriam Rol-Garcia Godfrey Smith Arne Hansen Torsten Christ Thomas Eschenhagen |
| author_facet | Marta Lemme Bärbel M. Ulmer Marc D. Lemoine Antonia T.L. Zech Frederik Flenner Ursula Ravens Hermann Reichenspurner Miriam Rol-Garcia Godfrey Smith Arne Hansen Torsten Christ Thomas Eschenhagen |
| author_sort | Marta Lemme |
| collection | DOAJ |
| description | Summary: 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. : Lemme et al. developed a human, atrial-like engineered heart tissue from hiPSCs that could be used as an in vitro model of the human atrium to evaluate selectivity of novel ion channel blockers for atrial fibrillation. Keywords: hiPSC-CMs, pluripotent stem cells, atrial differentiation, atrial myocytes, atrial-like cells, retinoic acid, engineered heart tissue, cardiac tissue engineering, atrial fibrillation |
| first_indexed | 2024-12-18T14:22:38Z |
| format | Article |
| id | doaj.art-9f074c489c1846e2b1fc42f04021209e |
| institution | Directory Open Access Journal |
| issn | 2213-6711 |
| language | English |
| last_indexed | 2024-12-18T14:22:38Z |
| publishDate | 2018-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Stem Cell Reports |
| spelling | doaj.art-9f074c489c1846e2b1fc42f04021209e2022-12-21T21:04:48ZengElsevierStem Cell Reports2213-67112018-12-0111613781390Atrial-like Engineered Heart Tissue: An In Vitro Model of the Human AtriumMarta Lemme0Bärbel M. Ulmer1Marc D. Lemoine2Antonia T.L. Zech3Frederik Flenner4Ursula Ravens5Hermann Reichenspurner6Miriam Rol-Garcia7Godfrey Smith8Arne Hansen9Torsten Christ10Thomas Eschenhagen11Institute of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Hamburg/Kiel/Lübeck, 20246 Hamburg, Germany; Clyde Biosciences Ltd, BioCity Scotland, Bo’Ness Road, Newhouse, Lanarkshire ML1 5UH, UKInstitute of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Hamburg/Kiel/Lübeck, 20246 Hamburg, GermanyInstitute of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Hamburg/Kiel/Lübeck, 20246 Hamburg, Germany; Department of Cardiology-Electrophysiology, University Heart Center, 20246 Hamburg, GermanyInstitute of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Hamburg/Kiel/Lübeck, 20246 Hamburg, GermanyInstitute of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Hamburg/Kiel/Lübeck, 20246 Hamburg, GermanyInstitute of Experimental Cardiovascular Medicine, University Heart Center Freiburg-Bad Krozingen, 79106 Freiburg, Germany; Institute of Physiology, Medical Faculty Carl Gustav Carus, TU Dresden, 01307 Dresden, GermanyDZHK (German Centre for Cardiovascular Research), Partner Site Hamburg/Kiel/Lübeck, 20246 Hamburg, Germany; Department of Cardiovascular Surgery, University Heart Center, 20246 Hamburg, GermanyClyde Biosciences Ltd, BioCity Scotland, Bo’Ness Road, Newhouse, Lanarkshire ML1 5UH, UKClyde Biosciences Ltd, BioCity Scotland, Bo’Ness Road, Newhouse, Lanarkshire ML1 5UH, UKInstitute of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Hamburg/Kiel/Lübeck, 20246 Hamburg, GermanyInstitute of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Hamburg/Kiel/Lübeck, 20246 Hamburg, GermanyInstitute of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Hamburg/Kiel/Lübeck, 20246 Hamburg, Germany; Corresponding authorSummary: 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. : Lemme et al. developed a human, atrial-like engineered heart tissue from hiPSCs that could be used as an in vitro model of the human atrium to evaluate selectivity of novel ion channel blockers for atrial fibrillation. Keywords: hiPSC-CMs, pluripotent stem cells, atrial differentiation, atrial myocytes, atrial-like cells, retinoic acid, engineered heart tissue, cardiac tissue engineering, atrial fibrillationhttp://www.sciencedirect.com/science/article/pii/S2213671118304314 |
| spellingShingle | Marta Lemme Bärbel M. Ulmer Marc D. Lemoine Antonia T.L. Zech Frederik Flenner Ursula Ravens Hermann Reichenspurner Miriam Rol-Garcia Godfrey Smith Arne Hansen Torsten Christ Thomas Eschenhagen Atrial-like Engineered Heart Tissue: An In Vitro Model of the Human Atrium Stem Cell Reports |
| title | Atrial-like Engineered Heart Tissue: An In Vitro Model of the Human Atrium |
| title_full | Atrial-like Engineered Heart Tissue: An In Vitro Model of the Human Atrium |
| title_fullStr | Atrial-like Engineered Heart Tissue: An In Vitro Model of the Human Atrium |
| title_full_unstemmed | Atrial-like Engineered Heart Tissue: An In Vitro Model of the Human Atrium |
| title_short | Atrial-like Engineered Heart Tissue: An In Vitro Model of the Human Atrium |
| title_sort | atrial like engineered heart tissue an in vitro model of the human atrium |
| url | http://www.sciencedirect.com/science/article/pii/S2213671118304314 |
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