On Friday 6 October 2023 Carla Cofiño Fabrés will defend her thesis titled "Advancements in molecular and bioengineering techniqes for driving maturation of human pluripotent stem-cell derived cardiac three-dimensional models".
During her PhD, Carla worked on the development of a 3D engineered heart tissue (EHT) platform that recapitulates aspects of the complex physiology of the human heart muscle. Specifically, EHT technology was combined with organ-on-chip to establish a heart-on-chip model featuring EHTs under microfluidic culture, while retaining the highly relevant readouts of the EHT-based technology. In this heart-on-chip system, she incorporated the direct interface between cardiomyocytes and endothelial cells, an interaction that plays a major role in cardiomyocyte’s function and metabolism in vivo, which could be recapitulated in this model. Additionally, by carefully curating the media composition to resemble the one in the in vivo adult human heart, a maturation media was developed that, when used in the EHTs, promotes one of the main developmental metabolic changes: the switch from glycolytic to oxidative metabolism, centered around fatty acid usage. Moreover, transcriptomic analysis by single-cell RNA sequencing during cardiac development in vitro and in these models helped elucidating key signaling and transcription factors that can be used to further modulate and improve cardiac specification and maturation in hPSC-based cardiac models. Ultimately, these results will contribute to improving cardiac health and disease modeling in vitro and toxicity screening.
