Year 3/NCE

The over-riding goal of this project was to identify and develop nutrient (culture medium) conditions that improve the metabolic behavior stem cell-derived cardiomyocytes. Unlike cells in the adult heart, cardiomyocytes derived from pluripotent stem cells do not rely on fat burning (or beta-oxidation) to generate energy. This difference limits the potential of stem cell technologies in translational and drug-discovery applications. In this project we identified key nutritional deficiencies in the way stem cells are converted to heart cells. By supplying more fat to cells, we were able to improve their maturity. Specifically, this fat promoted the functional development of mitochondria, which are the “engines” of cells and the primary site within cells where fat is burned. Inclusion of fat mixtures in stem cell cultures enhanced their metabolic behavior so that they can better mimic adult heart cells. In turn, this work will enable researchers and companies to more effectively use stem cell-derived cardiac cells for drug discovery, disease modeling, and regenerative medicine applications.