It also showed an improvement in functional class (although less pronounced in NYHA class IV) and improvement in quality of life, although it did not demonstrate improved survival.39 Fischer et al.40 performed intracoronary infusion of bone marrow-derived cells on 33 patients with dilated nonischemic cardiomyopathy and analyzed hemodynamics and cardiac function by Doppler at 3 months. There was an improvement in

global and segmental contractility, with Inhibitors,research,lifescience,medical a significant increase in LVEF (30.2%±10.9% to 33.4%±11.5%, P=.001). Dynamics showed a lower coronary vascular resistance index unchanged in the reference vessel diameter, which could result in improved micro- and macrovascular endothelial Inhibitors,research,lifescience,medical function; they also showed a significant decrease at 1 year in NT-proBNP levels (1610±993 to 1473±1147 pg/mL, P=0.038), a known neuroimmunomodulator with well-established prognostic

implications in patients with HF.40 Inflammatory Paracrine Response to Stem Cell Therapy Several studies have focused on the ability Inhibitors,research,lifescience,medical of stem cells to improve or regenerate myocardium by injecting cell suspensions containing either mixed or purified cellular population into the heart. Despite the apparent benefit of this experimental procedure, the mechanisms remain controversial and unclear, leaving large gaps in the understanding of the actual outcome of stem cell therapies and its future implications Inhibitors,research,lifescience,medical in the field of medicine. Few reports have focused on the immunologic aspects of the inflammatory paracrine response to stem cell therapy that might lead to improved cardiac function, cell proliferation, angiogenesis, or vasculogenesis by secreted Inhibitors,research,lifescience,medical chemical

mediators via inflammatory cell infiltration and immunologic reactions. Preclinical models have confirmed the main role of paracrine effects as part of stem cell therapy benefits, demonstrating attenuated apoptosis of endothelial cells and cardiomyocytes41 as well as cardiac function improvement42 and tissue perfusion related to angiogenesis and arteriogenesis.43 These effects are apparently significantly related Oxalosuccinic acid to lymphohistiocytic infiltration at stem cell injection sites.44 The importance of monocytes and macrophages in myocardial tissue healing and prevention of ventricular remodeling has been tested in several models45-46 and has shown that macrophages act as producing Selleckchem ROCK inhibitor factors that protect hypoxic cardiac cells from apoptosis.47 Some authors suggest that the beneficial action of stem cells depends on their ability to recruit lymphohistiocytic compounds more than on cell differentiation to new cardiomyocytes, and that the most important positive effects are related to the death of implanted cells in the site of transplantation rather than the intact stem cells by themselves (Figure 2).