Engineering human cardiac stem cells for therapeutic applications in heart disease

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The heart has minimal regenerative capacity and suffers permanent damage and muscle loss after an infarction. The exogenous use of stem cells to repair the damaged heart has a long history founded on the premise that the transplanted cells might have potent cardiomyogenic potential. As it has emerged that the adult stem cell types being used in fact have very little capacity to make new myocardium1, the very modest benefits achieved by these treatments are no longer surprising. However, in comparison to stem cells of adult origin, human embryonic and induced pluripotent stem cells (hPSCs) have the capacity to make all cell types including bona fide cardiomyocytes and therefore offer much more profound potential for cardiac regenerative medicine. As approximately one billion cardiomyocytes are lost following an infarction, an effective cell therapy may require not only efficient engraftment but also post-transplant expansion potential. Until recently the expansion of hPSC-derived cardiac progenitor cells (CPCs) was unachievable2, but using genetic manipulation this is now possible3. Taking a unique multidisciplinary approach, this project aims to overcome fundamental challenges by engineering cardiac cell identity (epigenetic status/gene expression) as well as the cells' biophysical microenvironment on transplantation, to deliver crucial advances in cardiac regenerative medicine.