expanded from cardiac biopsies by different protocols. 9, 10 Very recently, the first patients were treated with either cardiosphere-derived cardiac stem cells (CArdiosphere-Derived aUtologous stem CElls to reverse ventricUlar dySfunction [CADUCEUS trial], www. clinicaltrials. org/NCT00893360) or selected c-kit cardiac stem cells that were further expanded in vitro (www. clinicaltrials. org/NCT00474461).

Of note, multiple other (stem) cell types are currently being experimentally tested. Embryonic stem cells (ESCs) were among the most promising candidates for generating cardiac tissue, although ethical issues, immune tolerance, and teratoma formation are imposing challenges for using ESC as therapy (for review, see the work by Freund and Mummery11). The generation of patient-specific pluripotent stem cells by nuclear reprogramming of somatic cells by pluripotency genes provides an exciting new perspective. Reprogramming of murine fibroblasts by the combination of OCT3/4, SOX2, KLF4, and c-MYC was recently shown to generate pluripotent stem cells capable of postischemic contractile performance and in situ regeneration of cardiac, smooth muscle, and endothelial tissue in mouse models. 12 Thus, derivatives of pluripotent stem cells might be attractive for treating cardiac diseases, although specific additional challenges have been identified that preclude short-term application in clinical cell therapy. 11