Estudo pré-clínico de implante de células tronco hematopoéticas em camundongos com cardiopatia isquêmica induzida e tratados com fator de crescimento celular

Abstract

Several therapeutic alternatives have been employed in the therapy of patients with heart disease. In recent years, cellular therapy has emerged as a new strategy for ischemic heart disease and represents the most promising approach to treating these diseases. The literature suggests that the use of cell growth factor directs the HSC to the myocardium and facilitates the implantation and differentiation of the cells at the implant site, but few preclinical and clinical data were made for this cytokine. The objective proposed in this study was to characterize the role of G-CSF on cardiac remodeling in an experimental model of myocardial infarction induced in mice implanted with or without CTH. Was performed to obtain peripheral blood hematopoietic stem cells, prior to mobilization with G-CSF in inbred mice and the cells were implanted in different experimental groups. The cytokine TGF-β, IL-6 were measured by the technique of Enzime linked immunosorbent assay (ELISA) and IL-2, MCP-1, TNF-α, IL-10, IL-12, IFN-γ by Cytometric Bead Array (CBA). Histopathology of heart tissue was performed by hematoxylin-eosin (HE) and Masson's Malory. The measurement of cytokines was observed that the concentration of TGF-β decreased the serum of the experimental groups (IAM, IAM-PBS, IAM-CTH-GCSF and IAM-GCSF) compared to SHAM control group (p = 0.0470 ). The concentration of IL-6 showed an increase in the IAM-PBS group and IAM-CTH-G-CSF groups compared to SHAM and IAM-GCSF (p = 0.6053). Observed that IL-12 increased in the IAM-PBS group, the heart tissue in relation to the SHAM groups, IAM-CTH-GCSF and IAM-GCSF, and IFN-γ decreased in group IAM-CTH-GCSF and IAM-GCSF. Data from histopathological analysis showed no change in the SHAM group. On the other hand in the infarcted groups, without any treatment (IAM) and IAM-PBS, were identified, areas of vascular ectasia, disorganization in the direction of cardiac fibers, transmural scar, mild angiogenesis and necrosis with little inflammatory infiltrate. Groups IAM-CTH and IAM-CTH-GCSF had a moderate angiogenesis, healing areas, slight fibrosis, and inflammatory infiltrate with predominance of macrophages, plasma cells and histiocytes, with mild fibrosis, vascular ectasia and disorganization of the extracellular matrix. In the IAM-GCSF group, was observed a moderate angiogenesis, with a pronounced inflammatory infiltrate, characteristic of plasma cells, areas of calcification and extensive fibrosis. The G-CSF seems to have an important role in cardiac remodeling in an experimental model studied.