Stem Cell Reports (Jul 2016)

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

DOI
https://doi.org/10.1016/j.stemcr.2016.04.011
Journal volume & issue
Vol. 7, no. 1
pp. 29 – 42

Abstract

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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.