Human Pluripotent Stem Cells in Cardiovascular Research and Regenerative Medicine

Heart disease is one of the leading causes of mortality worldwide. Because adult cardiomyocytes (CMs) lack the ability to regenerate, malfunctions or significant loss of CMs due to disease or aging can lead to cardiac arrhythmias, heart failure, and subsequently death. Heart transplantation for patients with end stage heat failure is limited by the number of donor organs available. Cell-based therapies offer a promising alternative for myocardial repair, but there are significant challenges involved. The transplantation of human CMs, eg fetal CMs, is difficult for practical and ethical reasons, thus cells of noncardiac lineage, such as skeletal myoblasts (Murry et al., 1996; Menasche et al., 2003) and mesenchymal stem cells (Shake et al., 2002; Toma et al., 2002), have been considered as alternatives. Animal studies and clinical trials involving these cells have yielded conflicting results. Transplanted non-cardiac cells such as bone marrow-derived hematopoietic cells do not transdifferentiate into the cardiac lineage (Balsam et al., 2004; Murry et al., 2004). They also do not integrate into the host myocardium. For instance, the lack of electrical integration of skeletal myoblasts after their autologous transplantation into the myocardium resulted in the generation of malignant ventricular arrhythmias, which led to the premature termination of clinical trials involving skeletal myoblasts (Menasche et al., 2003; Smits et al., 2003). Therefore, an alternative cell source is needed.