Actions of stem cell derived paracrine factors on the heart. Stem cells transplanted into the myocardium release numerous factors that may act in an autocrine manner or paracrine manner to modulate the implanted cells themselves, or the endogenous cells of the heart, including cardiac myocytes, fibroblasts, endothelial cells, vascular smooth muscle cells, and cardiac stem cells. These factors include a variety of growth factors, cytokines, and extracellular matrix proteins that may lead to upregulation of several endogenous growth factors, cytokines, and extracellular matrix proteins, thereby tightly regulating neovascularization, protection against cell death, inflammation, fibrosis, contractility, bioenergetics, and endogenous repair. Regulation of these processes, either singly or in combination, by stem cell transplantation ultimately leads to improvement in left ventricular function following myocardial infarction. Future research in discovering novel stem-derived paracrine factors and their precise mechanistic roles in heart repair and fibrosis may ultimately lead to the generation of novel therapeutic agents for the treatment of heart failure.