Advancing cardiac safety and drug discovery screening using human stem cell-derived cardiomyocytes

Abstract

This thesis delves into the expansive utilization of both 2D and 3D human cardiac stem cell models for assessing cardiac safety and efficacy through a combination of in vitro and in silico methodologies. Various technological innovations are described in this thesis that led to cardiac in vitro models that are more scalable, reproducible and in which the cardiomyocytes are more mature.

The final chapter of this thesis presents a groundbreaking demonstration of how 3D human cardiac stem cell models can consistently reveal a disease phenotype that can be rescued through drug treatment. This represented a significant milestone in the use of these models for disease modeling, high-throughput screening, and potential regulatory approval.

Overall, the advancements detailed in this thesis have elevated the "technology readiness level" of these models, making them well-suited for use within the pharmaceutical industry. With continued progress, as outlined in this thesis, human cardiac stem cell models hold the potential to revolutionize drug discovery for cardiovascular diseases, safety testing, and personalized medicine.