title: Bone marrow endothelial progenitors are defective in systemic sclerosis.
abstract: OBJECTIVE
  Vascular abnormalities represent the main component of the pathobiology 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 numbers in the peripheral blood (PB) of SSc patients and to evaluate whether their status is related to impaired quantitative and/or qualitative aspects of the bone marrow (BM) microenvironment.
  
  
  METHODS
  Circulating EPCs from 62 SSc patients were evaluated by flow cytometry and characterized as CD45 negative and CD133 positive. BM EPCs, identified as CD133 positive, were isolated from 14 SSc patients and grown to induce endothelial differentiation. In addition, progenitor numbers 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 number was significantly increased in patients with early-stage disease but not in those with late-stage disease. All of the examined BM samples contained reduced numbers 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Ospedale G. Pini, University of Milan, Italy. delpapa@gpini.it
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Del Papa
authors.forename: Nadia
authors.initials: N
authors.lastname: Quirici
authors.forename: Davide
authors.initials: D
authors.lastname: Soligo
authors.forename: Cinzia
authors.initials: C
authors.lastname: Scavullo
authors.forename: Michela
authors.initials: M
authors.lastname: Cortiana
authors.forename: Chiara
authors.initials: C
authors.lastname: Borsotti
authors.forename: Wanda
authors.initials: W
authors.lastname: Maglione
authors.forename: Denise P
authors.initials: DP
authors.lastname: Comina
authors.forename: Claudio
authors.initials: C
authors.lastname: Vitali
authors.forename: Paolo
authors.initials: P
authors.lastname: Fraticelli
authors.forename: Armando
authors.initials: A
authors.lastname: Gabrielli
authors.forename: Agostino
authors.initials: A
authors.lastname: Cortelezzi
authors.forename: Giorgio
authors.initials: G
authors.lastname: Lambertenghi-Deliliers
mesh_terms: D000071916:AC133 Antigen; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005434:Flow Cytometry; D006023:Glycoproteins / Q000032:analysis; D006801:Humans; D017493:Leukocyte Common Antigens / Q000032:analysis; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000473:pathology*; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000473:pathology / Q000503:physiopathology; D010455:Peptides / Q000032:analysis; D012595:Scleroderma, Systemic / Q000097:blood / Q000473:pathology* / Q000503:physiopathology
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; D017493:Leukocyte Common Antigens