[Cardiac cell therapy: the puzzle is waiting to be solved]

Cell therapy has been proposed as an innovative hypothesis to treat acute myocardial infarction and heart failure. However, the mechanism by which stem cells could improve cardiac function remains unclear and many controversies have been arisen in interpretation of experimental and clinical data. Answering the five "WH questions" we discuss the process that has led to consider cell therapy as a new treatment option for myocardial tissue regeneration after ischemic damage. 1) Why should we use stem cells? The rationale derives from the disclosure that apoptosis and regeneration occur at the myocardial level and stem cells migrate from bone marrow to repopulate the damaged cardiac tissue. 2) Which are the most appropriate cells, delivery methods and therapeutic purposes? Adult stem cells can be mobilized or directly transplanted in human hearts to accomplish myocardioneogenesis, neoangiogenesis and/or paracrine effects. 3) Where should we transplant these cells? The infarct border zone seems to be the best place to home and differentiate transplanted cells hampering post-ischemic cardiac remodeling. 4) When should we perform cell therapy? Cell therapy should be performed during or after an acute myocardial infarction: best setting and timing still need to be precisely addressed. 5) Who might be the suitable patient? Further multicenter randomized trials with adequate patient selection are needed to answer this crucial question.