Embryonic stem cells (ESCs) were first derived in the early 1980s simultaneously by 2 independent groups,1,2 and because of their plasticity and potentially unlimited capacity for self-renewal, they were predicted to transform research in mammalian development, genetics, stem cell biology, and regenerative medicine. However, it quickly became apparent that although ESCs would become an invaluable tool to study development and stem cell biology, translating their promise into the clinics would be problematic. Twenty-eight years after the first report describing mouse ESCs and 10 years after the successful derivation of human ESCs, the US Food and Drug Administration approved the first human ESC-related clinical trial for spinal cord injuries this year; however, it is now on its second clinical hold, and no subjects have yet been enrolled. Although this delay in translation to human trials is likely multifactorial, major obstacles remain with the clinical use of ESCs over ethical issues, oncogenic risk, and the fact that ESC derivatives for tissue repair involve the use of allogeneic cells that can lead to rejection of mismatched cellular grafts. The oncogenic risk associated with stem cell therapies is no longer just theoretical. This year, the first report of a patient who developed multiple tumors in his brain and spinal cord after receiving fetal neural stem cells was published.3 Thus, therapeutic application of pluripotent stem cells (PSCs), particularly in the cardiovascular field, requires further advancement and new approaches such as that described by Zwi et al4 in this issue of Circulation . Article see p 1513 Although how to minimize the oncogenic risk of PSCs continues to be an area of intense research, investigators have long sought to overcome the ethical and immunologic issues surrounding ESCs by creating autologous PSCs. Initial attempts to create these cells involved nuclear cloning technology in which …