HEART2BEAT · Advanced human models of the heart to understand cardiovascular disease

Cardiovascular diseases (CVD) are the cause of the highest mortality and morbidity rates worldwide and are expected to increase in coming years, leading to epidemic proportions. Traditional experimental in vitro and animal models are not predictive enough, which hampers the emergence of novel therapies for treatment of CVD. Consequently, there is an urgent need to establish realistic human models that lead to a better understanding of CVD, providing the opportunity to identify and validate druggable targets. In Heart2Beat I will develop innovative human heart models for mimicking cardiovascular disease. I will use an innovative in-air microfluidic platform for ultra-high throughput encapsulating of human pluripotent stem cells in microgels to generate self-organised multicellular 3D human cardiac organoids that replicate the architectural design of the human heart. Furthermore, I will integrate and develop innovative technologies from the fields of human stem cell biology and engineering to create 3D (micro)-engineered heart tissues, coupled to a versatile and automated microfluidic platform, enabling assessment of multifunctional analysis (e.g., contraction, relaxation, metabolism, morphology). Finally, I will build a functional human mini-heart with the capacity to pump fluid, the main function of the human heart and then assess clinically relevant readouts in healthy and diseased conditions. These first-of-its kind advanced 3D human cardiac models and platforms are complementary to each other and form a highly innovative and comprehensive pipeline for modelling human CVD, enabling (ultra)high throughput screening and in-depth multifunctional pre-clinical analysis of healthy and diseased heart tissues. Successful implementation of Heart2Beat will provide insight into mechanisms of disease and will initiate a paradigm shift for personalised medicine and drug discovery, leading to tailor-made therapy for patients suffering from CVD.