Advances in our understanding of the molecular basis of ventricular dysfunction and the evolution of increasingly efficient gene transfer technology have placed congestive heart failure within reach of gene-based therapy. The road from basic mechanisms to clinical gene therapy for cardiac disease has been long and arduous, with intense animal and cellular experimentation that has often failed.

The application of cell-based therapies has followed a different trajectory. Only a few months elapsed between the first reports that showed beneficial effects of bone-marrow-derived stem cells after myocardial infarction in rodents and the initiation of clinical trials. Since then, a large number of trials have been conducted using stem cells derived from a variety of sources, the success of which has been quite modest. As we pointed out in our editorial in January 2007 (Nadal-Ginard and Fuster [2007] Nat Clin Pract Cardiovasc Med 4: 1) the challenges for cell therapy remain at the basic mechanistic level: identifying suitable cells for effective cardiomyocyte regeneration, recreating the appropriate microenvironment for enabling progenitor cells to survive and differentiate, and developing safe and effective methods of delivery.