Human Engineered Heart Tissue: Analysis of Contractile Force
| Autor: | David Letuffe-Brenière, K. Breckwoldt, Christiane Neuber, Ingra Mannhardt, Anika Benzin, Thomas Eschenhagen, Marc N. Hirt, Arne Hansen, Alexandra Eder, Birgit Klampe, Sebastian Schaaf, Herbert Schulz, Tessa Werner, Torsten Christ, Alessandra Moretti, Thomas G. Schulze, Norbert Huebner |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Inotrope Sarcomeres medicine.medical_treatment Cellular differentiation Induced Pluripotent Stem Cells Biology Biochemistry Sarcomere Article Contractility 03 medical and health sciences Tissue engineering Genetics medicine Myocyte Humans Myocytes Cardiac Induced pluripotent stem cell lcsh:QH301-705.5 lcsh:R5-920 Tissue Engineering Growth factor Myocardium Cell Differentiation Heart Cell Biology Anatomy Myocardial Contraction Cell biology Mitochondria 030104 developmental biology lcsh:Biology (General) Cardiovascular and Metabolic Diseases lcsh:Medicine (General) Developmental Biology |
| Zdroj: | Stem Cell Reports Stem Cell Reports, Vol 7, Iss 1, Pp 29-42 (2016) |
| ISSN: | 2213-6711 |
| Popis: | Summary 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. Graphical Abstract Highlights • Engineered heart tissues (EHTs) from hiPSC-CM are generated with high reproducibility • EHTs show aligned cardiomyocytes with organized sarcomeres and immature t tubules • Spontaneous beating is regulated by both, membrane- and calcium-clock mechanisms • EHTs respond to physiological and pharmacological interventions like human heart tissue Hansen and Eschenhagen and colleagues describe the analysis of contractile force in human engineered heart tissue from hiPSC. The physiological and pharmacological characterization of EHTs revealed a high degree of similarity to human heart tissue, indicating that human EHTs might be useful for preclinical drug testing and disease modeling. |
| Databáze: | OpenAIRE |
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