Cell therapy for the treatment of coronary heart disease: a critical appraisal.

Randomized, controlled clinical trials have demonstrated that cell therapy can improve the recovery of cardiac function in patients after acute myocardial infarction (AMI). Trial results are inconsistent, however, and uncertainty persists regarding the mechanism of action and prospect of cell therapy for patients with heart disease. This Review examines the results from the first-generation trials and discusses procedure-related variables that could have determined treatment outcomes. Obvious issues, including optimal timing of cell transfer, dose, and delivery methods are being investigated in ongoing second-generation trials. These studies aim to refine the protocols and identify the patients who will benefit most from cell therapy. Third-generation trials will address the current limitations of cell therapy, such as cell retention and cell survival after transplantation, and impaired cell functionality in patients with advanced cardiovascular disease. The secretion of factors with paracrine effects by the transplanted cells is an increasingly recognized phenomenon. Identification of these factors, by secretome analyses and bioinformatic approaches, could advance protein-based therapies to promote healing and inhibit pathological remodeling of the heart after AMI. The identification of reliable sources of pluripotent stem cells and their differentiation into mature cardiac cell types could ultimately enable regeneration of the infarcted heart.