The Mechanisms of Cell Therapy for Clinical Investigations: An Urgent Need for Large-Animal Models

Evidence from experiments performed in animal models and from early-stage clinical trials demonstrate that the contractile performance of hearts with severe ischemic injury can be improved by transplanting a variety of cell types into the injured heart.^1-5 As a result of these investigations progenitor cells have emerged as a promising therapeutic agent both for limiting postinfarction left-ventricular (LV) remodeling and for improvingcardiac performance in hearts with severe LV dysfunction secondary to other diseases, such as dilated cardiomyopathy and concentric LV hypertrophy. ^{6, 7} Some of the most encouraging clinical results were obtained in the SCIPIO trial ⁴, which investigated the use of autologous cardiacprogenitor cells (CPCs) in patients with severe LV dysfunction undergoing coronary artery bypass graft surgery. Although the small patient population and open-label design preclude definitive mechanistic conclusions, CPCs infusion was associated with significant improvements in LV ejection fraction from before treatment to 4 months afterward, and even greater improvement was observed at 12 months. These and other promising results could soon lead to the initiation of more definitive, large-scale, phase 2 clinical trials.