Derivation of ventrical and atrial cardiomyocytes and maturation using biowires

Tissue engineering using cardiomyocytes derived from human pluripotent stem cells holds a promise to revolutionise drug discovery, but only if limitations related to cardiac chamber specification and platform versatility can be overcome. We describe here a scalable tissue cultivation platform that is cell source agnostic and enables drug testing under electrical pacing. The plastic platform enabled on-line, non-invasive, recording of passive tension, active force, contractile dynamics and Ca2+ transients, as well as endpoint assessments of action potentials and conduction velocity. By combining directed cell differentiation with electrical field conditioning, we engineered electrophysiologically distinct atrial and ventricular tissues with chamber-specific drug responses and gene expression. We report, for the first time, engineering of heteropolar cardiac tissues containing distinct atrial and ventricular ends, and demonstrate their spatially confined responses to serotonin and ranolazine. Uniquely, electrical conditioning for up to 8 months enabled modeling of polygenic left ventricular hypertrophy starting from patient cells. human embryonic stem cells were cultured under conditions to generate either atrial or ventricle cardiomyocytes. The cardiomyocytes were placed into biowires that simulate normal cardiac sinus rhythm. Cell were harvested and assessed after a period of culture with or without electrical stimulation.