title: Impaired endothelium-mesenchymal stem cells cross-talk in systemic sclerosis: a link between vascular and fibrotic features.
abstract: BACKGROUND
  To assess if an impaired cross-talk between endothelial cells (ECs) and perivascular/multipotent mesenchymal stem cells (MSCs) might induce a perturbation of vascular repair and leading to a phenotypic switch of MSC toward myofibroblast in Systemic Sclerosis (SSc).
  
  
  METHODS
  We investigated different angiogenic and profibrotic molecules in a tridimentional matrigel assay, performing co-cultures with endothelial cells (ECs) and bone marrow derived MSCs from patients and healthy controls (HC). After 48 hours of co-culture, cells were sorted and analyzed for mRNA and protein expression.
  
  
  RESULTS
  ECs-SSc showed a decreased tube formation ability which is not improved by co-cultures with different MSCs. After sorting, we showed: i. an increased production of vascular endothelial growth factor A (VEGF-A) in SSc-MSCs when co-cultured with SSc-ECs; ii. an increased level of transforming growth factor beta (TGF-β) and platelet growth factor BB (PDGF-BB) in SSc-ECs when co-cultured with both HC- and SSc-MSCs; iii. an increase of TGF-β, PDGF-R, alpha smooth muscle actin (α-SMA) and collagen 1 (Col1) in both HC- and SSc-MSCs when co-cultured with SSc-ECs.
  
  
  CONCLUSIONS
  We showed that during SSc, the ECs-MSCs crosstalk resulted in an altered expression of different molecules involved in the angiogenic processes, and mainly SSc-ECs seem to modulate the phenotypic switch of perivascular MSCs toward a myofibroblast population, thus supporting the fibrotic process.
authors.forename: Paola
authors.initials: P
authors.lastname: Cipriani
authors.forename: Paola
authors.initials: P
authors.lastname: Di Benedetto
authors.forename: Piero
authors.initials: P
authors.lastname: Ruscitti
authors.forename: Antonio Francesco
authors.initials: AF
authors.lastname: Campese
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Liakouli
authors.forename: Francesco
authors.initials: F
authors.lastname: Carubbi
authors.forename: Ilenia
authors.initials: I
authors.lastname: Pantano
authors.forename: Onorina
authors.initials: O
authors.lastname: Berardicurt
authors.forename: Isabella
authors.initials: I
authors.lastname: Screpanti
authors.forename: Roberto
authors.initials: R
authors.lastname: Giacomelli
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000077214:Becaplermin; D015153:Blotting, Western; D002450:Cell Communication; D002478:Cells, Cultured; D018920:Coculture Techniques; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D000090602:Collagen Type I, alpha 1 Chain; D042783:Endothelial Cells / Q000378:metabolism* / Q000502:physiology; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000502:physiology; D008875:Middle Aged; D058628:Myofibroblasts / Q000378:metabolism; D018919:Neovascularization, Physiologic; D020574:Proto-Oncogene Proteins c-sis / Q000235:genetics / Q000378:metabolism; D017479:Receptors, Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D045743:Scleroderma, Diffuse / Q000378:metabolism* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D000199:Actins; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D020574:Proto-Oncogene Proteins c-sis; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; D000077214:Becaplermin; C000588866:KDR protein, human; D017479:Receptors, Platelet-Derived Growth Factor; D040301:Vascular Endothelial Growth Factor Receptor-2