Stem Cell Therapy in Acute Myocardial Infraction

Introduction The incidence of congestive heart failure (HF) is increasing with epidemic proportions, occurring most frequently in patients with structural heart disease resulting from myocardial infarction (MI). The process of cardiac remodeling that provides the substrate for HF results from fibrotic scar formation that replaces regions of myocyte necrosis. In addition, surviving myocytes undergo hypertrophy, which may be initially beneficial but subsequently transitions to a maladaptive process in which myocytes become vulnerable to apoptosis. The heart dilates due to infarct expansion, with wall thinning and dilatation of the ventricle, hyperplasia of fibroblasts, and scar formation, which results in changes to its geometry and loss of contractile function. Recently, mitotic cardiomyocytes and endogenous cardiac stem cells have been identified within the mammilian heart 2-4 suggesting that the heart is not a terminally differentiated organ. However, it is evident that these endogenous repair mechanisms are insufficient to allow a complete structural and functional recovery of the heart from a MI. Cellular regenerative approaches hold great promise to prevent remodeling and progression to HF in ischemically damaged hearts which has resulted in two closely related avenues of research. One approach has focused on the biology of endogenous stem or precursor cells that reside in the adult heart . Other researchers have used a variety of exogenous progenitor cells and stem cells as transplants into regions of ischemic damaged myocardium. In experimental models the cell types which have been investigated include fetal and neonatal cardiomyocytes, embryonic stem cell derived myocytes, tissue engineered contractile grafts, skeletal myoblasts, several cell types derived from adult bone marrow, and cardiac stem cells . This approach termed, cellular cardiomyoplasty , is currently under active investigation in large animal models, and has already prompted clinical trials .