Human Engineered Heart Tissue: Analysis of Contractile Force

Ingra Mannhardt, Kaja Breckwoldt, David Letuffe-Brenière, Sebastian Schaaf, Herbert Schulz, Christiane Neuber, Anika Benzin, Tessa Werner, Alexandra Eder, Thomas Schulze, Birgit Klampe, Torsten Christ, Marc N. Hirt, Norbert Huebner, Alessandra Moretti, Thomas Eschenhagen, Arne Hansen

Research output: Contribution to journalArticlepeer-review

269 Scopus citations

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.

Original languageEnglish
Pages (from-to)29-42
Number of pages14
JournalStem Cell Reports
Volume7
Issue number1
DOIs
StatePublished - 12 Jul 2016
Externally publishedYes

Fingerprint

Dive into the research topics of 'Human Engineered Heart Tissue: Analysis of Contractile Force'. Together they form a unique fingerprint.

Cite this