Abstract-Bone marrow mononuclear cells (BM-MNCs) have successfully been used as a therapy for the improvement of left ventricular (LV) function after myocardial infarction (MI). It has been suggested that paracrine factors from BM-MNCs may be a key mechanism mediating cardiac protection. We previously performed microarray analysis and found that the pleiotropic cytokine interleukin (IL)-10 was highly upregulated in human progenitor cells in comparison with adult endothelial cells and CD14 ϩ cells. Moreover, BM-MNCs secrete significant amounts of IL-10, and IL-10 could be detected from progenitor cells transplanted in infarcted mouse hearts. Specifically, intramyocardial injection of wild-type BM-MNCs led to a significant decrease in LV end-diastolic pressure (LVEDP) and LV end-systolic volume (LVESV) compared to hearts injected with either diluent or IL-10 knock-out BM-MNCs. Furthermore, intramyocardial injection of wild-type BM-MNCs led to a significant increase in stroke volume (SV) and rate of the development of pressure over time (ϩdP/dt) compared to hearts injected with either diluent or IL-10 knock-out BM-MNCs. The IL-10 -dependent improvement provided by transplanted cells was not caused by reduced infarct size, neutrophil infiltration, or capillary density, but rather was associated with decreased T lymphocyte accumulation, reactive hypertrophy, and myocardial collagen deposition. These results suggest that BM-MNCs mediate cardiac protection after myocardial infarction and this is, at least in part, dependent on IL-10. Key Words: acute myocardial infarction Ⅲ remodeling Ⅲ growth factors/cytokines Ⅲ cell therapy B one marrow-derived progenitor cells have been used clinically to improve left ventricular (LV) function in patients after acute myocardial infarction (MI), 1-4 however the exact mechanisms for this improvement in cardiac function have not clearly been defined. Several mechanisms have been proposed to explain the beneficial effects of this cell-based therapy including cell transdifferentiation, cell fusion, and the release of paracrine growth factors and cytokines. In support of the latter mechanism, various cytokines and growth factors from transplanted progenitor cells have been shown to be important in progenitor cell-mediated cardiac protection such as basic fibroblast growth factor, vascular endothelial growth factor, stromal-derived factor, 5,6 angiopoietin-1, interleukin (IL)-1, tumor necrosis factor-␣, 7,8 hepatocyte growth factor, insulin-like growth factor-1, thymosin 4, 8 secreted frizzled related protein 2, 9 IL-6, placental growth factor, transforming growth factor, monocyte chemoattractant protein-1, platelet-derived growth factor, plasminogen activator, and metalloproteinase-9. 10 We previously performed microarray analysis on peripheral blood-derived cultured human precursor cells 11 and found one paracrine factor highly expressed, the pleiotropic cytokine, IL-10. IL-10 is expressed and secreted by a variety of cell types such as T cells, monocytes/macrophages, dendritic cells, ...