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.; Hübner, Norbert; Moretti, Alessandra; Eschenhagen, Thomas und Hansen, Arne (2016): Human Engineered Heart Tissue: Analysis of Contractile Force. In: Stem Cell Reports, Bd. 7, Nr. 1: S. 29-42

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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 2213-6711
• Sprache: Englisch