Grant: Project Grant

Heart attacks damage heart muscle, replacing it with non-beating scar tissue. Damaged hearts can be repaired by injecting heart muscle cells called cardiomyocytes. Cardiomyocytes made from induced pluripotent stem cells show the best results, but only a portion of the injected cells survive. Furthermore, cells that survive often interfere with electrical function of the heart. A solution to these problems is to mature stem cell-derived cardiomyocytes in the lab beforehand, as more mature cells do better once transplanted. However, existing technologies do not produce highly mature stem cell-derived cardiomyocytes in the quantities needed to repair a heart, which has stifled progress towards cell therapy. We will address this need using engineered screening systems and artificial intelligence (AI) approaches developed by our team. As proof-of-principle, we used these approaches to invent a cocktail to nourish stem cell-derived cardiomyocytes that makes them more mature than the best cocktails available currently. We also engineered materials that promote stem cell growth better than standard materials. In this project, we will build on our previous work to find cocktails and materials that improve cardiomyocyte maturation assessed in multiple ways that are important for function, including their structure, gene expression, contraction, and electrical properties. Guided by AI, hundreds of possible recipes will be assessed for the best overall performance in advancing cardiomyocyte maturity. Finally, the best combinations of cocktails and materials will be used to produce highly-mature cardiomyocytes for injection into damaged guinea pig hearts, an excellent model to test the survival and function of the transplanted cells using state-of-the-art medical imaging and functional testing. The knowledge and technologies developed here will provide new insights and strategies to generate cardiomyocytes towards the treatment of heart failure, a growing epidemic in Canada.