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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. and Breckwoldt, K. and Letuffe-Brenière, D. and Schaaf, S. and Schulz, H. and Neuber, C. and Benzin, A. and Werner, T. and Eder, A. and Schulze, T. and Klampe, B. and Christ, T. and Hirt, M.N. and Huebner, N. and Moretti, A. and 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
Publisher:Cell Press / Elsevier
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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