Universität zu Köln

Mannhardt, Ingra, Breckwoldt, Kaja, Letuffe-Breniere, David, Schaaf, Sebastian, Schulz, Herbert, Neuber, Christiane, Benzin, Anika, Werner, Tessa ORCID: 0000-0002-7789-6816, Eder, Alexandra, Schulze, Thomas, Klampe, Birgit, Christ, Torsten, Hirt, Marc N., Huebner, Norbert, Moretti, Alessandra ORCID: 0000-0001-5782-7832, Eschenhagen, Thomas and Hansen, Arne (2016). Human Engineered Heart Tissue: Analysis of Contractile Force. Stem Cell Rep., 7 (1). S. 29 - 43. CAMBRIDGE: CELL PRESS. ISSN 2213-6711

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Abstract

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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Mannhardt, Ingra UNSPECIFIED UNSPECIFIED UNSPECIFIED Breckwoldt, Kaja UNSPECIFIED UNSPECIFIED UNSPECIFIED Letuffe-Breniere, David UNSPECIFIED UNSPECIFIED UNSPECIFIED Schaaf, Sebastian UNSPECIFIED UNSPECIFIED UNSPECIFIED Schulz, Herbert UNSPECIFIED UNSPECIFIED UNSPECIFIED Neuber, Christiane UNSPECIFIED UNSPECIFIED UNSPECIFIED Benzin, Anika UNSPECIFIED UNSPECIFIED UNSPECIFIED Werner, Tessa UNSPECIFIED orcid.org/0000-0002-7789-6816 UNSPECIFIED Eder, Alexandra UNSPECIFIED UNSPECIFIED UNSPECIFIED Schulze, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Klampe, Birgit UNSPECIFIED UNSPECIFIED UNSPECIFIED Christ, Torsten UNSPECIFIED UNSPECIFIED UNSPECIFIED Hirt, Marc N. UNSPECIFIED UNSPECIFIED UNSPECIFIED Huebner, Norbert UNSPECIFIED UNSPECIFIED UNSPECIFIED Moretti, Alessandra UNSPECIFIED orcid.org/0000-0001-5782-7832 UNSPECIFIED Eschenhagen, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Hansen, Arne UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-269940
DOI:	10.1016/j.stemcr.2016.04.011
Journal or Publication Title:	Stem Cell Rep.
Volume:	7
Number:	1
Page Range:	S. 29 - 43
Date:	2016
Publisher:	CELL PRESS
Place of Publication:	CAMBRIDGE
ISSN:	2213-6711
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CELL-DERIVED CARDIOMYOCYTES; PLURIPOTENT STEM-CELLS; TORSADE-DE-POINTES; CARDIAC-HYPERTROPHY; ACTION-POTENTIALS; RISK-ASSESSMENT; IN-VITRO; MATURATION; CHANNELS; MYOCARDIUM Multiple languages Cell & Tissue Engineering; Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/26994