Generation, characterization, and potential therapeutic applications of cardiomyocytes from various stem cells

Heart failure is one of the leading causes of death worldwide. Myocardial cell transplantation emerges as a novel therapeutic strategy for heart failure, but this approach has been hampered by severe shortage of human cardiomyocytes. We have recently induced mouse embryonic stem cells to differentiate into embryoid bodies and eventually, cardiomyocytes. Here, we address recent advancements in cardiomyocyte differentiation from cardiac stem cells and pluripotent stem cells. We highlight the methodologies, using growth factors, endoderm-like cell cocultures, small molecules, and biomaterials, in directing the differentiation of pluripotent stem cells into cardiomyocytes. The characterization and identification of pluripotent stem cell-derived cardiomyocytes by morphological, phenotypic, and functional features are also discussed. Notably, increasing evidence demonstrates that cardiomyocytes may be generated from the stem cells of several tissues outside the cardiovascular system, including skeletal muscles, bone marrow, testes, placenta, amniotic fluid, and adipose tissues. We further address the potential applications of cardiomyocytes derived from various kinds of stem cells. The differentiation of stem cells into functional cardiomyocytes, especially from an extra-cardiac stem cell source, would circumvent the scarcity of heart donors and human cardiomyocytes, and, most importantly, it would offer an ideal and promising cardiomyocyte source for cell therapy and tissue engineering in treating heart failure.