TY - JOUR
T1 - Human Engineered Heart Tissue
T2 - 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 - Publisher Copyright:
© 2016 The Author(s)
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.
UR - https://www.scopus.com/pages/publications/84975508034
U2 - 10.1016/j.stemcr.2016.04.011
DO - 10.1016/j.stemcr.2016.04.011
M3 - Article
C2 - 27211213
AN - SCOPUS:84975508034
SN - 2213-6711
VL - 7
SP - 29
EP - 42
JO - Stem Cell Reports
JF - Stem Cell Reports
IS - 1
ER -