Impaired In Vivo Neovascularization Capacity of Endothelial Progenitor Cells in Patients With Systemic Sclerosis

摘要

Objective. Defective vasculogenesis is thought to play a role in the pathogenesis of systemic sclerosis (SSc). We undertook this study to explore the in vivo functional capacity of CD34+CD133+CD309+ endothelial progenitor cells (EPCs) in SSc patients. Methods. CD 133+ cells and EPCs were enumerated by flow cytometry. Immunomagnetically sorted circulating CD133+ cells from 16 patients with SSc and 12 healthy subjects, as well as murine colon carcinoma CT-26 cells, were transplanted beneath the skin of SCID mice. Tumor volume and blood vessel density were measured 10 days later. Human EPC incorporation into the vascular wall was evaluated using tumor sections double stained for mouse CD31 and human CD31. Results. The number of CD133+ cells and EPCs was significantly decreased in SSc patients as compared to healthy controls (P = 0.001 and P = 0.02, respectively), while the proportion of EPCs in CD133+ cells was similar between the 2 groups. CT-26 cells produced markedly stronger tumor growth and neovessel formation when transplanted with CD133+ cells from healthy subjects than when transplanted with CD133+ cells from SSc patients (P = 0.001 and P = 0.008, respectively). Tumors from mice that received transplants of CT-26 cells and SSc-derived CD 133+ cells formed fewer vessels incorporating human EPC-derived mature endothelial cells than did tumors from mice that received transplants of CT-26 cells and CD133+ cells from healthy control subjects (P = 0.0002).