Human engineered heart tissue: analysis of contractile force

Mannhardt, I.; Breckwoldt, K.; Letuffe-Brenière, D.; Schaaf, S.; Schulz, H.; Neuber, C.; Benzin, A.; Werner, T.; Eder, A.; Schulze, T.; Klampe, B.; Christ, T.; Hirt, M.N.; Huebner, N.; Moretti, A.; Eschenhagen, T.; Hansen, A.

Human engineered heart tissue: analysis of contractile force

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Item Type:	Article
Title:	Human engineered heart tissue: analysis of contractile force
Creators Name:	Mannhardt, I., Breckwoldt, K., Letuffe-Brenière, D., Schaaf, S., Schulz, H., Neuber, C., Benzin, A., Werner, T., Eder, A., Schulze, T., Klampe, B., Christ, T., Hirt, M.N., Huebner, N., Moretti, A., Eschenhagen, T. and Hansen, A.
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.
Keywords:	Cell Differentiation, Heart, Induced Pluripotent Stem Cells, Mitochondria, Myocardial Contraction, Myocardium, Myocytes, Cardiac, Sarcomeres, Tissue Engineering
Source:	Stem Cell Reports
ISSN:	2213-6711
Publisher:	Cell Press / Elsevier
Volume:	7
Number:	1
Page Range:	29-42
Date:	12 July 2016
Official Publication:	https://doi.org/10.1016/j.stemcr.2016.04.011
PubMed:	View item in PubMed

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