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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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