Human embryonic stem cell-derived cardiomyocytes for heart therapies

Cardiovascular diseases remain the leading cause of mortality and morbidity worldwide. Despite substantial improvements in acute management, survivors of myocardial infarction often progress to heart failure. Since adult cardiomyocytes (CMs) do not regenerate, their loss permanently compromises myocardial contractile function. Heart transplantation is currently the last resort for end-stage heart failure, but is hampered by a severe shortage of donor organs and rejection. Cell-based therapies are a promising alternative: Various cell types such as human fetal CMs, skeletal muscle myoblasts and smooth muscle cells have been tested but these approaches are also limited by cell availability or side effects (e.g. due to their non-cardiac identity). In recent years, clinical studies exploiting adult bone marrow mesenchymal stem cells for transplantation in patients with coronary artery disease have reported favorable outcomes but their cardiomyogenic ability is limited. By contrast, human embryonic stem cells (hESCs), derived from the inner cell mass of blastocyst-stage embryos, are pluripotent and can self-renew and differentiate into all cell types including CMs. Furthermore, hESC-derived CMs (hESC-CMs) are viable human heart cells that can functionally integrate with the recipient organ after transplantation. This article reviews the current state and hurdles of hESC-CM research, as well as their therapeutic potentials and limitations.