Development of 3D Vascularized Human iPS-Derived Heart on a Chip

Heart disease is considered one of the leading causes of the death worldwide. Animal models and in vitro cellular models have thus far failed to efficiently mimic human heart disease, showing a limited response or poor prognostic value for drug development and toxicity screening. Human iPS-derived cardiomyocytes (iPS-CMs) have some advantages over current models. However, structural and functional maturation of iPS-CMs remains a key challenge for applications in disease modeling, drug screening, and regenerative medicine. Here we report on the development of human heart-like organoids with structural and functional properties similar to a mature heart composed of 3D co-cultures of iPS-CMs and cardiac endothelial cells. Complex three dimensional, vascularized organoids formed in Tissue Dynamics micro-well bioreactor within 20 hours allowing us to monitor heart-on-chip function continuously over several days.

Analysis of our iPS-CMs showed the physiological attributes of an adult heart: Basal heart rate of 66±5 beats per minute (bpm), achievement of spontaneous synchronal beating within 3 days of seeding, steady beating and a first indication of what may be a secondary stimuli. Epinephrine exposure increased the rate to 88±7 bmp and 18% stronger contraction, while amiodarone reduced the rate to 52±4 bmp and 28% weaker contraction. In summary, our iPS-CMs have very similar metabolic profile and force/activity ratio compared to primary cells. We devise our heart-on-a-chip model for heart disease research, cardiotoxicity screening, drug target discovery and drug efficacy testing.