The human heart has a limited regenerative capacity. Therefore, severe cardiac injury leads to fibrosis and subsequent remodeling of the heart and development of heart failure. Human embryonic stem cells (hESCs) can be differentiated to heart cells and can provide a source to restore heart function after an injury. The CIRM New Faculty Award afforded us to look into this issue carefully. We successfully generated specialized heart muscle cells (referred to as cardiomyocytes) from hESCs. We performed full characterization of these cells including their electrical properties and the genes and proteins they express as they develop from a progenitor state to mature cardiomyocytes.
Considering the heart has different types of cardiomyocytes in its different compartments, we generated hESC lines that express a distinct fluorescent reporter protein upon differentiation into different types of cardiomyocytes. This strategy allowed up to isolate the different types of cardiomyocytes and assess their properties both in a dish as well as in small animal models. We have also performed transplantation studies in large animal models, using pigs since their cardiac physiology closely resembles that of human’ hearts. We transplanted approximately 400 million hESC-derived cardiomyocytes in pig’s hearts while maintaining them on immunosuppressive therapy. Eight weeks after transplantation, we noticed the engraftment of the transplanted cells with large patches of muscle that could be potentially improve the heart function.
We believe that we have made significant contribution to this field and our results are very promising. We plan to continue these studies and move onto preclinical studies by preparing a tissue-engineered scaffold that contains millions of left ventricular cardiomyocytes for transplantation into large animals after an experimental myocardial infarction. We are optimistic that our findings will change clinical practice in the near future.