Bone marrow endothelial progenitors are defective in systemic sclerosis

Objective. Vascular abnormalities represent the main component of the pathobiol. of systemic sclerosis (SSc), progressing from structural derangements of the microcirculation with abortive neoangiogenesis to final vessel loss. Since circulating endothelial progenitor cells (EPCs) are important in the vascular repair process, we undertook this study to examine their nos. in the peripheral blood (PB) of SSc patients and to evaluate whether their status is related to impaired quant. and/or qual. aspects of the bone marrow (BM) microenvironment. Methods. Circulating EPCs from 62 SSc patients were evaluated by flow cytometry and characterized as CD45 neg. and CD133 pos. BM EPCs, identified as CD133 pos., were isolated from 14 SSc patients and grown to induce endothelial differentiation. In addn., progenitor nos. and functional properties of hematopoietic and stromal compartments were analyzed by various assays. Results. We found that EPCs were detectable in the PB of patients with SSc, and their no. was significantly increased in patients with early-stage disease but not in those with late-stage disease. All of the examd. BM samples contained reduced nos. of EPCs and stromal cells, both of which were functionally impaired. Both endothelial and stromal progenitors expressed vascular endothelial growth factor receptor, indicating that BM is strongly induced to differentiate into the endothelial lineage; furthermore, only BM EPCs from patients with early disease led to endothelial differentiation in vitro. Conclusion. This study provides the first demonstration that in SSc, there is a complex impairment in the BM microenvironment involving both the endothelial and mesenchymal stem cell compartments and that this impairment might play a role in defective vasculogenesis in scleroderma. [on SciFinder (R)]