Enhanced angiogenic potency of monocytic endothelial progenitor cells in patients with systemic sclerosis

Monocytic EPCs were enriched and enumerated using a culture of peripheral blood mononuclear cells and platelets on fibronectin in 23 patients with SSc, 22 patients with rheumatoid arthritis (RA), and 21 healthy controls. To assess the capacity of monocytic EPCs to promote vascular formation and the contribution of vasculogenesis to this process, we used an in vitro co-culture system with human umbilical vein endothelial cells (HUVECs) on Matrigel？ and an in vivo murine tumor neovascularization model.Monocytic EPCs were significantly increased in SSc patients than in RA patients or healthy controls (P = 0.01 for both comparisons). Monocytic EPCs derived from SSc patients promoted tubular formation in Matrigel？ cultures more than those from healthy controls (P = 0.007). Transplantation of monocytic EPCs into immunodeficient mice resulted in promotion of tumor growth and blood vessel formation, and these properties were more prominent in SSc than healthy monocytic EPCs (P = 0.03 for both comparisons). In contrast, incorporation of SSc monocytic EPCs into the tubular structure was less efficient in vitro and in vivo, compared with healthy monocytic EPCs.SSc patients have high numbers of aberrant circulating monocytic EPCs that exert enhanced angiogenesis but are impaired in vasculogenesis. However, these cells apparently cannot overcome the anti-angiogenic environment that characterizes SSc-affected tissues.Systemic sclerosis (SSc) is a multi-system connective tissue disease characterized by excessive fibrosis and microvascular abnormalities. SSc vasculopathy mainly affects small arteries, causing reduced blood flow and tissue ischemia, which leads to Raynaud's phenomenon, digital ulcers, and gangrene [1]. The pathogenesis of SSc vasculopathy is not fully understood, but several lines of evidence have shown that the primary mechanism involves enhanced vascular injury, occurring as a result of an inflammatory-immune response and ischemia-reperfusion reactions [2,3]. On t