Advancements in molecular and bioengineering techniques for driving maturation of human pluripotent stem cell-derived cardiac three-dimensional models
Carla Cofiño Fabrés is a PhD student in the department Applied Stem Cell Technologies. (Co)Promotors are prof.dr. P.C.J.J. Passier and dr. V. Schwach from the faculty Science & Technology.
Cardiovascular disease (CVD) remains a leading cause of death worldwide. Developing new drugs for CVD still remains costly and time-consuming, mainly due to the low efficacy and predictivity of new targets on the animal models used during the pre-clinical phase. Therefore, there is a need for alternative technologies that can be used to study and treat CVD. In this thesis, essential steps required to enhance the utility and success of human pluripotent stem cell derived cardiomyocytes (hPSC-CMs) for drug screening and discovery applications, as well as for studying human cardiac development and disease, are described. We discuss how to generate certain cardiac cell types, such as atrial cardiomyocytes, using specialized protocols, and how to use applied single cell transcriptomic analysis to decipher mechanisms governing cardiac specification in vitro. Additionally, state-of-the art 3D culture methods, such as Engineered Heart Tissues (EHTs) and their incorporation in a heart-on-chip microfluidic system are developed to better recapitulate aspects of the complex physiology of the human heart. We also use these systems to further elucidate and mature the state of the hPSC-CMs and to evaluate the cardiotoxic effects of anticancer drugs. In summary, this thesis focuses entirely on the application and improvement of in vitro models for the heart, with stem cell technology at its core.