Despite recent advances in medical and surgical treatment, cardiovascular diseases (CVD) remain the number one cause of morbidity and mortality in the US. 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 CVD (1
). In adult tissues such as those in the heart, the capacity for self-regeneration is limited. One promising approach is to inject stem cells into damaged hearts, 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 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 six months post intracoronary injection of mononuclear bone marrow cells (BMC) into infarcted heart, no significant improvement in left ventricular ejection fraction (LVEF) was observed (5
). Similarly, Jassen et al.
failed to detect any considerable improvement in ventricular function at four months after injection of mononuclear BMC (6
). By contrast, Schachinger et al.
found that 59 patients suffering from 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 LVEF and end-systolic volume (7
). Other trials are summarized in . 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.
Intracoronary Injection of Bone Marrow Cells in Patients with Ischemic Heart Disease.