Bone marrow endothelial progenitors are defective in systemic sclerosis.
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.
Del Papa
Nicoletta
N
Ospedale G. Pini, University of Milan, Italy. delpapa@gpini.it
Quirici
Nadia
N
Soligo
Davide
D
Scavullo
Cinzia
C
Cortiana
Michela
M
Borsotti
Chiara
C
Maglione
Wanda
W
Comina
Denise P
DP
Vitali
Claudio
C
Fraticelli
Paolo
P
Gabrielli
Armando
A
Cortelezzi
Agostino
A
Lambertenghi-Deliliers
Giorgio
G
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
D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; D017493:Leukocyte Common Antigens