Randomized Clinical Trials in Stem Cell Therapy for the Heart - Old and New Types of Cells for Cardiovascular Repair

Abstract

Recent advances in reperfusion strategies have dramatically reduced early mortality after acute myocardial infarction (AMI), but as a result there is a higher incidence of heart failure among survivors. Optimal medical therapy and device implantation can improve the prognosis and the quality of life of these patients. Nevertheless, mortality and rehospitalization rates are still high and entail an overwhelming cost. The field of cardiac cell therapy has emerged as a new alternative in this situation, and has made rapid progress. Its final goal is to repair the damaged myocardium and to restore cardiac function. Nevertheless, this goal is hindered by the massive loss of cardiomyocytes after an AMI (in the order of 1 billion cells) and because ischemic myocardium loses cellular and extracellular signals which guide stem cells to the cardiac lineage or to the secretion of paracrine factors (Wollert & Drexler, 2010). Studies evaluating this new approach during the last 15 years have overall succeeded to a greater or lesser extent, and evidence available so far is encouraging. Phase I and II randomized clinical trials (RCT) indicate that cell therapy is a safe treatment which can improve cardiac function after AMI and in the chronic phase of coronary artery disease (CAD). Trial results are not uniform, however, probably due 1) to a lack of standardization of cell isolation and delivery procedures, 2) to the absence of a universally accepted nomenclature, and 3) to the large number of stem cell types under investigation in different clinical settings. Nevertheless, these inconsistencies can be avoided or reduced if classical scientific methodology is followed. Although considered a relatively new field of research, stem cell experimentation must invariably walk on the path of the scientific method. Since Aristotle s time, scientific method has been used as a way to ask and answer scientific questions by making observations and doing experiments. It includes a series of steps, i.e. 1) asking a question, 2) doing background research, 3) constructing a hypothesis, 4) testing the hypothesis by doing an experiment, 5) analyzing the data and drawing a conclusion, and 6) communicating the results.