Human Engineered Heart Tissue: Analysis of Contractile Force
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Human Engineered Heart Tissue: Analysis of Contractile Force. / Mannhardt, Ingra; Breckwoldt, Kaja; Letuffe-Brenière, David; Schaaf, Sebastian; Schulz, Herbert; Neuber, Christiane; Benzin, Anika; Werner, Tessa; Eder, Alexandra; Schulze, Thomas; Klampe, Birgit; Christ, Torsten; Hirt, Marc N; Huebner, Norbert; Moretti, Alessandra; Eschenhagen, Thomas; Hansen, Arne.
in: STEM CELL REP, Jahrgang 7, Nr. 1, 12.07.2016, S. 29-42.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Human Engineered Heart Tissue: Analysis of Contractile Force
AU - Mannhardt, Ingra
AU - Breckwoldt, Kaja
AU - Letuffe-Brenière, David
AU - Schaaf, Sebastian
AU - Schulz, Herbert
AU - Neuber, Christiane
AU - Benzin, Anika
AU - Werner, Tessa
AU - Eder, Alexandra
AU - Schulze, Thomas
AU - Klampe, Birgit
AU - Christ, Torsten
AU - Hirt, Marc N
AU - Huebner, Norbert
AU - Moretti, Alessandra
AU - Eschenhagen, Thomas
AU - Hansen, Arne
N1 - Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.
PY - 2016/7/12
Y1 - 2016/7/12
N2 - 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.
AB - 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.
KW - Journal Article
U2 - 10.1016/j.stemcr.2016.04.011
DO - 10.1016/j.stemcr.2016.04.011
M3 - SCORING: Journal article
C2 - 27211213
VL - 7
SP - 29
EP - 42
JO - STEM CELL REP
JF - STEM CELL REP
SN - 2213-6711
IS - 1
ER -