utologous cell therapy is a promising approach to treat myocardial dysfunction after ischemic injury. Cell therapeutic approaches in cardiovascular disease are therefore of fundamental interest and focus of intense basic and clinical investigation.A number of randomized clinical trials on autologous cell treatment for acute myocardial infarction have shown at least transient improvements in left ventricular function. 1,2 Other trials, however, did not find significant benefits of cell therapy. 3,4 For cell therapy of chronic ischemic heart disease, the results are scarce and even more controversial. [5][6][7] To understand the challenges and problems of cell therapy, we need to consider a few critical points: cell type, disease setting and cell condition. (1) The choice of cell types and the relevant functions of therapeutic cells; (2) the clinical setting, ie, acute vs chronic ischemic heart disease, which, among other things, relates to the presence or absence of ischemia as a homing cue; and (3) the cellular condition that critically influences the performance of therapeutic cells. Finally, we discuss ex vivo modification strategies to improve cell function.
Cell Types and FunctionDifferent cell types have been used for the treatment of acute myocardial infarction 8,9 and chronic ischemic cardiomyopathy. 5 However, the most potent cell type and the mechanisms by which transplanted cells transmit their therapeutic effects remains elusive. In most of the clinical studies the investigators have opted for bone marrow mononuclear cells (BMC), 1 but also progenitor cells from peripheral blood 10 and mesenchymal stem cells (MSC) 11,12 have been used, because of their ease of availability from autologous sources. The clinical setting acute vs chronic ischemia critically influences the choice of a therapeutic cell type. The optimal period for cell treatment of the acutely infarcted heart with BMC has been narrowed to >5 days following myocardial infarction. 2 MSC, which require a prolonged initial culturing step, can be expanded in vitro, stored and used in the allogenic setting as a result of their low immunogenecity. 11 Both, bone marrow and peripheral blood progenitors are a heterogenous cell population, which precludes the direct comparison of efficacy and potency. While Cell therapy is a promising approach to improve cardiac function in patients with ischemic heart disease. Beneficial effects of cell therapy have been shown in experimental studies and clinical trials. However, with current treatment strategies the therapeutic effect is limited. In the current article, critical aspects of cell therapy are discussed: cell type, the state of ischemic heart disease and the condition of cells at the time of treatment. Because treatment options of native cells by systemic pharmacotherapy are limited, we propose a concept of ex vivo preconditioning to overcome functional cell impairment and to enhance cell-based regenerative approaches. (Circ J 2009; 73: 2179 -2182