Engineered Heart Muscle Models in Phenotypic Drug Screens

Classical drug development is compromised by considerable clinical failure of promising drug candidates after decades of costly preclinical work. Failure can be because of previously unrecognized safety concerns or more commonly lack of clinical efficacy. Classical drug discovery and safety pharmacology programs rely heavily on well-established in vitro and preclinical animal models. The availability of human pluripotent stem cells and the possibility to direct them into any somatic cell type suggest that a paradigm shift in drug development may be possible and timely, with the opportunity to test safety and efficacy of candidate drugs on the human target cells and tissue. However, there is considerable uncertainty as to whether human models would only qualify as replacement for well-established tools or add substantially more information to the preclinical data package, to facilitate translation of more promising drug candidates into clinical practice. This chapter provides an overview of tissue-engineered macro-scale heart muscle models for applications in drug discovery and safety pharmacology.