Propriedades funcionais de células-tronco mesenquimais vasculares em ratos com diabetes mellitus experimental

Abstract

Macroangiopathy and accelerated atherosclerosis are important outcomes in patients with diabetes mellitus (DM) and contribute to the high morbidity/mortality observed in this disease. Vascular mesenchymal stem cells contribute to the physiology of the vascular wall and could be altered in DM. Objectives: To evaluate several biological properties of arterial and venous vascular mesenchymal stem cells (vMSCs) in a rat model of streptozotocin-induced DM. Methods: After 08 weeks of DM induction, untreated, treated and control diabetic rats had their blood glucose and body weight evaluated weekly. At the end, the aorta and inferior vena cava were excised and processed for histology and extraction of vascular mononuclear cells. A pool of these cells was seeded for a colony-forming unit-fibroblast (CFU-F) assay to estimate the number of vMSCs. The remaining cells were expanded to assess their proliferation rate, phenotypic expression of c-Kit and CD45, a hematopoietic cell marker, as well as their osteogenic, adipogenic and endothelial-like differentiation abilities. Vascular histological analysis was also performed to quantify vascular fibrosis with picrosirius red, a collagen marker. Results: DM rats showed intense hyperglycemia and low body weight after 08 weeks. Insulin treatment (8IU dose) was able to prevent hyperglycemia and body weight loss. CFU-F numbers, c-Kit/CD45 expression and proliferation rates were not different for arterial and venous vMSCs in all experimental groups. In contrast, arterial vMSCs from untreated DM rats showed a lower ability to differentiate into osteogenic, adipogenic, and endothelial lineages. Insulin treatment prevented the differentiation deficit. The aortas from DM rats showed signs of macroangiopathy, as they showed increased collagen labeling compared to the aortas from control and DM treated animals. Conclusion: The findings suggest, for the first time, that in rats with chronic DM, vMSCs exhibit alterations in several differentiation properties, which may be implicated in the pathogenesis of diabetic macroangiopathy.