Ischemic heart disease remains the leading cause of congestive heart failure (CHF). The prevalence of CHF has increased dramatically over the preceding decade, with now more than 10% of the United States population over 65 years of age carrying the diagnosis. Because of the aging population, combined with the alarming increase in diabetes in the United States, the number of Americans with CHF is projected to increase to more than 6 million people by the year 2030.

Despite the improved outcome in patients with acute myocardial infarction (AMI) treated with mechanical reperfusion therapy, a substantial mortality and morbidity persists. Recent clinical trials of AMI that tested enhanced reperfusion strategies have not demonstrated significant improvements in mortality (1,2). Further complicating our attempts to minimize myocardial tissue loss in patients with AMI is the lack of significant progress in encouraging patients with symptoms of acute ischemia to present earlier. The time to presentation for patients enrolled in clinical trials is nearly 3 hours after symptom onset and has not changed over the past decade. These findings suggest that, for us to significantly improve the mortality of cardiovascular disease, a shift towards preserving and/or regenerating cardiac function following the ischemic insult must occur.

Because we may have reached a limit in our attempts to minimize myocardial necrosis using state-of-the-art reperfusion strategies in patients presenting with AMI, significant interest has evolved in optimizing or regenerating myocardial tissue following the ischemic event. Although the mechanisms are still under investigation (3, 4, 5, 6), the development of CHF following AMI involves more than just the loss of contractile tissue; CHF also is determined partly by the ventricular remodeling that occurs in response to myocardial necrosis. The inflammatory response to myocardial necrosis leads to infarct expansion, dilatation of the left ventricular (LV) cavity, and replacement of cardiomyocytes with fibrous tissue.

Currently available therapies to alter the remodeling process and the progression to CHF remain limited, and absolute death rates from CHF continue to rise. Furthermore, although cardiac transplantation is a definitive therapy for severe end-stage CHF, it remains limited in number and, in some instances, simply trades one set of symptoms for another. This unmet need of current therapies to preserve myocardial function following myocardial infarction (MI) has led to the identification of new treatment paradigms that focus on preventing myocardial cell death during MI, attenuating pathologic remodeling, and regenerating myocardium.

Autologous cell transplantation provides one mechanism through which this daunting task can be achieved (15). The goal of this review is to summarize the literature on cell therapy for the treatment of LV dysfunction, and to attempt to give a clinical perspective on the potential of this evolving therapeutic strategy.

Cell therapy is receiving growing attention as a potential therapeutic option to preserve and/or regenerate contractile tissue and counter ventricular remodeling. To combat heart failure using cell therapy, the objective is to reverse myocardial thinning, dilatation, and decreased function by replacing a critical number of lost cardiomyocytes with contractile cells transplanted into the infarct zone (7). Cellular transplantation has focused on several distinct cell types for use in experimental and first clinical pilot trials, including differentiated cells such as skeletal myoblasts, cardiac myocytes, smooth muscle cells, and cardiac fibroblasts. Other studies have focused on the viability of stem cells derived from the bone marrow, embryonic, and umbilical chord tissue (8, 9, 10, 11). Currently, the primary questions being addressed by experimentation are (a) Which cells (or combination of cells) are best suited for cardiac regeneration and vascularization?; and (b) Which signals can be used to recruit them? (10). Moreover, cell survival must be optimized once engraftment has taken place. The answers to these questions are complex and take into
account practical and safety concerns. Additionally, the different routes of cell delivery via intravenous infusion, or catheter-assisted intracoronary and intramyocardial injection, can produce varying outcomes (12, 13, 14). Concurrent clinical investigations will help to assess the impact that cell therapy has on either preserving or improving cardiac function during or following AMI.