Stem cells in cardiac repair in an inflammatory microenvironment.

Despite advances in clinical interventions, drug therapy and preventative strategies for cardiovascular disease, heart disease remains the number one cause of death in the United States. A major cause of heart failure leading to death is myocardial ischemic disease. Terminal heart failure can be salvaged in some cases by cardiac transplants, but this therapeutic approach is limited by lack of supply, high cost, and problems with immunosuppression. An attractive alternative approach proposed over the last 1-2 decades is the replacement of myocardium at the level of the myocyte, which has focused on stem cell therapy. This form of therapy has been successful for hematopoietic replacement. Similar therapy has been proposed to treat hearts ravaged by ischemic necrosis and apoptosis. However, the experimental studies have not been effectively translated to patients with myocardial infarction or heart failure. This review discusses the current literature and points out key studies that are required for future directions, focusing on key roles for microenvironmental factors, such as cytokines, in stem cells responses when placed at sites of cardiac injuries. In the case of mesenchymal stem cells (MSCs), they exert both immune- enhancer and -suppressor functions, which are referred to as immune plasticity. This type of immune properties by MSCs is significant to therapeutic outcomes. Thus, the plasticity of MSCs, with regards to immune responses, has to be considered carefully in tissue repair and replacement and in gene delivery systems. The route by which cytokines are delivered as adjuvant to cell therapy, or as methods to mobilize stem cells, will show varied results, depending on the degree of injury, underlying clinical disorders and other diverse parameters, such as ethnicity, age and genomic profile. In addition to MSCs, roles exist for other stem cells, such as those from placenta, cord blood, hematopoietic stem/progenitor cells and cardiac stem cells.