Comparison of imaging techniques for tracking cardiac stem cell therapy.

A growing number of exciting animal and preclinical studies are beginning to reveal the immense potential in stem cell–based therapies, particularly in the area of treating cardiovascular diseases. However, to evaluate the efficacy of these treatments in clinical trials, the transplanted stem cells must be monitored quantitatively and qualitatively in vivo. To date, several noninvasive imaging approaches have been used to follow the fate of stem cells in vivo. Here, we review the basic principles of the current techniques for cardiac stem cell tracking, compare the relative advantages and disadvantages of these imaging modalities, and discuss the future prospects for cardiac stem cell trafficking. Despite recent advances in medical and surgical treatments, cardiovascular diseases remain the number one cause of morbidity and mortality in the United States. The societal and financial consequences are tremendous. For example, the American Heart Association estimates the economic costs of cardiovascular diseases in the United States for 2007 at $431.8 billion, including direct and indirect costs incurred by cardiovascular diseases (1). In adult tissues such as those of the heart, the capacity for selfregeneration is limited. One promising approach is to inject into damaged hearts stem cells, which could potentially repopulate the myocardium, induce neovascularization, and lead to significant functional improvement (2). Encouraging animal studies from the late 1990s and early 2000s have led to the initiation or completion of several human clinical trials involving transplantation of bone marrow stem cells, skeletal myoblasts, or circulating progenitor cells into the heart (3). However, contradictory results from recent studies that used different origins of therapeutic stem cells and different routes of cell delivery highlight the need to elucidate the molecular mechanisms by which stem cells actually contribute to cardiac functional recovery (4). For instance, Lunde et al. showed that at 6 mo after intracoronary injection of mononuclear bone marrow cells into the infarcted heart, no significant improvement in left ventricular ejection fraction was observed (5). Similarly, Janssens et al. failed to detect any considerable improvement in ventricular function at 4 mo after injection of mononuclear bone marrow cells (6). By contrast, Schachinger et al. found that 59 patients with acute myocardial infarction who were treated with direct intracoronary infusion of either circulating progenitor cells or bone marrow–derived progenitor cells showed significant improvements in left ventricular ejection fraction and end-systolic volume (7). Clearly, these mixed results on cardiac stem cell therapy are both perplexing to scientists and frustrating to patients. Further studies are therefore urgently needed to clarify the discrepancies in clinical trials and validate the efficacy of cardiac repair using therapeutic stem cells.