Cardiac regeneration by cell therapy

Abstract

During the last fifty years, we have seen enormous progress in the prevention and treatment of acute myocardial infarction (MI), one of the most prominent diseases in the Western world. As a result, the incidence and prevalence of acute MI has gradually declined, and mortality and morbidity have been reduced. However, due to the increased lifespan post MI, the incidence of congestive heart failure (CHF) is rapidly increasing. Heart failure directly results from the death or dysfunction of cardiomyocytes and an inability of the heart to effectively regenerate this damaged region. These pathophysiologic events lead to a process of cardiac remodeling that involves fibrosis, changes in wall stress, scar expansion and - if the injury is large enough - heart failure. Although pharmacological treatment has significantly improved survival, with further progression of heart failure, heart transplantation is the only current definitive treatment option. At present, no approved clinical therapy treats the underlying defect in ischemic injury: the death of cardiomyocytes. As a result, heart failure has become the most prevalent cardiovascular disease in this century and will likely strain health care costs as patients live longer. In the last few years, cell therapy has emerged as a possible treatment for many types of disease. Transplanting cells that are able to differentiate and replace dead or dysfunctional cardiomyocytes and vasculature, that may prevent transition to adverse remodeling or can induce cardiac regeneration via paracrine mechanisms could be a definitive therapy for cardiac ischemic injury. The first study, describing the feasibility of transplanting myoblasts, the precursor cells of skeletal muscle, after MI was published in 1992. In 1998, the first pre-clinical therapeutic benefit of transplanted myoblasts was demonstrated. Since then, a number of cell types have been tranplanted into injured myocardium with promising results.