title: Orbital Fibroblasts From Graves' Orbitopathy Patients Share Functional and Immunophenotypic Properties With Mesenchymal Stem/Stromal Cells.
abstract: OBJECTIVE
  In Graves' orbitopathy (GO), inflammation and expansion of the retrobulbar tissue are the result of a pathophysiologic process in which orbital fibroblasts (GO-Fs) are considered the central cell type. However, in a previous study we observed that GO-Fs expressed some of the consensus surface markers described for mesenchymal stem/stromal cells (MSC). In this study, we further elucidate the stem cell characteristics of GO-Fs by comparing them with orbital fat-derived mesenchymal stem cells.
  
  
  METHODS
  We enriched primary human GO-MSCs and GO-Fs simultaneously from the same retrobulbar fat biopsies obtained during decompression surgery of GO patients. The biological characteristics of donor-matched GO-MSCs and -Fs were compared along criteria that define MSC: fibroblast-like growth, MSC surface marker profile, multilineage differentiation potential, and immunomodulatory functions.
  
  
  RESULTS
  Application of a standardized isolation and expansion protocol yielded GO-MSCs, which showed plastic adherent fibroblast-like morphology and proliferated and produced hyaluronan similarly to GO-Fs. Both GO-MSCs and GO-Fs expressed orbital fat-derived stem cell surface markers CD29, CD44, CD71, CD73, CD90, CD105, and CD166 and were negative for CD31, CD34, CD45, CD146, and Stro-1 after ex vivo expansion. Further, GO-MSCs and GO-Fs displayed adipogenic, osteogenic, chondrogenic, myogenic, and neuronal differentiation, although GO-Fs with a lower capacity. In addition, when compared to GO-MSCs, the GO-Fs showed reduced T-cell suppression and secreted reduced amounts of IL-6, suggesting a lower immunosuppressive potential.
  
  
  CONCLUSIONS
  The in vitro data obtained in this study provide the first experimental evidence that orbital fibroblasts derived from retrobulbar fat of GO patients share biological characteristics with MSCs. These findings provide new insight into the biology of key cells in GO.
authors.affiliation: Department of Otorhinolaryngology University of Duisburg-Essen, Essen, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Brandau
authors.affiliation: Department of Otorhinolaryngology University of Duisburg-Essen, Essen, Germany.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Bruderek
authors.affiliation: Department of Otorhinolaryngology University of Duisburg-Essen, Essen, Germany 2Department of Ophthalmology, Molecular Ophthalmology Group, University of Duisburg-Essen, Essen, Germany.
authors.forename: Khaleda
authors.initials: K
authors.lastname: Hestermann
authors.affiliation: Department of Ophthalmology, Molecular Ophthalmology Group, University of Duisburg-Essen, Essen, Germany.
authors.forename: Gina-Eva
authors.initials: GE
authors.lastname: Görtz
authors.affiliation: Department of Ophthalmology, Molecular Ophthalmology Group, University of Duisburg-Essen, Essen, Germany.
authors.forename: Mareike
authors.initials: M
authors.lastname: Horstmann
authors.affiliation: Department of Otorhinolaryngology University of Duisburg-Essen, Essen, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Mattheis
authors.affiliation: Department of Otorhinolaryngology University of Duisburg-Essen, Essen, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Lang
authors.affiliation: Department of Ophthalmology, Molecular Ophthalmology Group, University of Duisburg-Essen, Essen, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Eckstein
authors.affiliation: Department of Ophthalmology, Molecular Ophthalmology Group, University of Duisburg-Essen, Essen, Germany.
authors.forename: Utta
authors.initials: U
authors.lastname: Berchner-Pfannschmidt
mesh_terms: D050156:Adipogenesis / Q000276:immunology*; D000273:Adipose Tissue / Q000276:immunology / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism*; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D005347:Fibroblasts / Q000276:immunology* / Q000473:pathology; D005434:Flow Cytometry; D049970:Graves Ophthalmopathy / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology*; D009915:Orbit; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
chemical_list: D015415:Biomarkers