title: Impairment of endothelial cell differentiation from bone marrow-derived mesenchymal stem cells: new insight into the pathogenesis of systemic sclerosis.
abstract: OBJECTIVE
  Systemic sclerosis (SSc) is a disorder characterized by vascular damage and fibrosis of the skin and internal organs. Despite marked tissue hypoxia, there is no evidence of compensatory angiogenesis. The ability of mesenchymal stem cells (MSCs) to differentiate into endothelial cells was recently demonstrated. The aim of this study was to determine whether impaired differentiation of MSCs into endothelial cells in SSc might contribute to disease pathogenesis by decreasing endothelial repair.
  
  
  METHODS
  MSCs obtained from 7 SSc patients and 15 healthy controls were characterized. The number of colony-forming unit-fibroblastoid colonies was determined. After culture in endothelial-specific medium, the endothelial-like MSC (EL-MSC) phenotype was assessed according to the surface expression of vascular endothelial growth factor receptors (VEGFRs). Senescence, chemoinvasion, and capillary morphogenesis studies were also performed.
  
  
  RESULTS
  MSCs from SSc patients displayed the same phenotype and clonogenic activity as those from controls. In SSc MSCs, a decreased percentage of VEGFR-2+, CXCR4+, VEGFR-2+/CXCR4+ cells and early senescence was detected. After culturing, SSc EL-MSCs showed increased expression of VEGFR-1, VEGFR-2, and CXCR4, did not express CD31 or annexin V, and showed significantly decreased migration after specific stimuli. Moreover, the addition of VEGF and stromal cell-derived factor 1 to cultured SSc EL-MSCs increased their angiogenic potential less than that in controls.
  
  
  CONCLUSIONS
  Our data strongly suggest that endothelial repair may be affected in SSc. The possibility that endothelial progenitor cells could be used to increase vessel growth in chronic ischemic tissues may open up new avenues in the treatment of vascular damage caused by SSc.
authors.affiliation: University of L'Aquila, L'Aquila, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Cipriani
authors.forename: S
authors.initials: S
authors.lastname: Guiducci
authors.forename: I
authors.initials: I
authors.lastname: Miniati
authors.forename: M
authors.initials: M
authors.lastname: Cinelli
authors.forename: S
authors.initials: S
authors.lastname: Urbani
authors.forename: A
authors.initials: A
authors.lastname: Marrelli
authors.forename: V
authors.initials: V
authors.lastname: Dolo
authors.forename: A
authors.initials: A
authors.lastname: Pavan
authors.forename: R
authors.initials: R
authors.lastname: Saccardi
authors.forename: A
authors.initials: A
authors.lastname: Tyndall
authors.forename: R
authors.initials: R
authors.lastname: Giacomelli
authors.forename: M Matucci
authors.initials: MM
authors.lastname: Cerinic
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D016922:Cellular Senescence; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000378:metabolism; D042783:Endothelial Cells / Q000502:physiology*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000473:pathology* / Q000502:physiology; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D010641:Phenotype; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism; D012595:Scleroderma, Systemic / Q000473:pathology / Q000503:physiopathology*; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology
chemical_list: C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D019718:Receptors, CXCR4; D040262:Receptors, Vascular Endothelial Growth Factor