Endothelial outgrowth cells regulate coagulation, platelet accumulation, and respond to tumor necrosis factor similar to carotid endothelial cells

内皮生长细胞调节凝血、血小板积聚,并对肿瘤坏死因子作出类似于颈动脉内皮细胞的反应

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作者:Jeremy J Glynn, Monica T Hinds

Abstract

Endothelial cells (ECs) are central regulators of hemostasis, inflammation, and other vascular processes. ECs have been used to cover vascular graft materials in an attempt to improve the biological integration of the grafts with the surrounding tissue. Although EC seeded grafts demonstrated improved patency, the invasive nature of EC harvest has limited the clinical translation of this technique. Endothelial outgrowth cells (EOCs) can be derived from circulating endothelial progenitor cells, which are noninvasively isolated from a peripheral blood draw. Although EOCs have been presumed to regulate hemostasis and inflammation similarly to arterial ECs, there has been limited research that directly compares EOCs to arterial ECs, particularly using pairs of donor-matched cells. This study provides a multifaceted characterization of hemostasis regulation by baboon EOCs and carotid ECs, both in the presence and absence of an inflammatory stimulus, tumor necrosis factor α (TNFα). The expression of genes involved in thrombosis and inflammation was highly similar between ECs and EOCs at a basal state and following TNFα stimulation. ECs and EOCs activated similar levels of protein C and Factor X (FX) at a basal state. Following TNFα treatment, EOCs had less of an increase in tissue factor activity than ECs. Cell-seeded expanded polytetrafluoroethylene vascular grafts demonstrated no significant differences between ECs and EOCs in platelet accumulation or fibrinogen incorporation in a baboon femoral arteriovenous shunt loop. This work demonstrates that EOCs regulate thrombus formation and respond to an inflammatory stimulus similar to ECs, and supports utilizing EOCs as a source for an autologous endothelium in tissue engineering applications.

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