Atrial-like Engineered Heart Tissue: An In Vitro Model of the Human Atrium
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Atrial-like Engineered Heart Tissue: An In Vitro Model of the Human Atrium. / Lemme, Marta; Ulmer, Bärbel M; Lemoine, Marc D; Zech, Antonia T L; Flenner, Frederik; Ravens, Ursula; Reichenspurner, Hermann; Rol-Garcia, Miriam; Smith, Godfrey; Hansen, Arne; Christ, Torsten; Eschenhagen, Thomas.
In: STEM CELL REP, Vol. 11, No. 6, 11.12.2018, p. 1378-1390.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Atrial-like Engineered Heart Tissue: An In Vitro Model of the Human Atrium
AU - Lemme, Marta
AU - Ulmer, Bärbel M
AU - Lemoine, Marc D
AU - Zech, Antonia T L
AU - Flenner, Frederik
AU - Ravens, Ursula
AU - Reichenspurner, Hermann
AU - Rol-Garcia, Miriam
AU - Smith, Godfrey
AU - Hansen, Arne
AU - Christ, Torsten
AU - Eschenhagen, Thomas
N1 - Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.
PY - 2018/12/11
Y1 - 2018/12/11
N2 - 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.
AB - 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.
KW - Journal Article
U2 - 10.1016/j.stemcr.2018.10.008
DO - 10.1016/j.stemcr.2018.10.008
M3 - SCORING: Journal article
C2 - 30416051
VL - 11
SP - 1378
EP - 1390
JO - STEM CELL REP
JF - STEM CELL REP
SN - 2213-6711
IS - 6
ER -