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Mesenchymal Stem Cell–Like Properties of Orbital Fibroblasts in Graves’ Orbitopathy

Kozdon, K; Fitchett, C; Rose, GE; Ezra, DG; Bailly, M; (2015) Mesenchymal Stem Cell–Like Properties of Orbital Fibroblasts in Graves’ Orbitopathy. Investigative Ophthalmology & Visual Science , 56 (10) pp. 5743-5750. 10.1167/iovs.15-16580. Green open access

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Abstract

PURPOSE. Graves’ orbitopathy (GO) is a sight-threatening autoimmune disorder causing extraocular muscle fibrosis, upper lid retraction and eye bulging due to orbital fat expansion. These clinical features are mediated by aspects of orbital fibroblasts differentiation, including adipogenesis and fibrosis. Our previous work suggested that this dual phenotype might be a manifestation of mixed cell populations, partially linked to the expression of mesenchymal stem cell (MSC) marker CD90. Thus, we set out to determine whether GO orbital fibroblasts displayed MSC properties. METHODS. Control and GO orbital fibroblasts previously characterized for CD90 and CD45 expression were analyzed by flow cytometry for classical MSC positive (CD73, CD105) and negative (CD14, CD19, HLA-DR, and CD34) markers. Graves’ orbitopathy fibroblasts were tested further for their ability to undergo lineage specific differentiation following standard protocols. RESULTS. Control and GO fibroblasts strongly expressed CD73 and CD105, with a higher percentage of positive cells and stronger expression levels in GO. Neither cell type expresses CD14, CD19, and HLA-DR. Protein CD34 was expressed at low levels by 45% to 70% of the cells, with its expression significantly lower in GO cells. Graves’ orbitopathy fibroblasts displayed features of osteogenesis (calcium deposits, and osteocalcin [BGLAP] and osteonectin [SPARC] expression), chondrogenesis (glycosaminoglycan production; SOX9 and aggrecan [ACAN] expression), myogenesis (α-smooth muscle actin expression), and neurogenesis (β-III tubulin expression) upon differentiation. CONCLUSIONS. Our findings suggest that orbital fibroblasts contain a population of cells that fulfil the criteria defining MSC. This subpopulation may be increased in GO, possibly underlying the complex differentiation phenotype of the disease

Type: Article
Title: Mesenchymal Stem Cell–Like Properties of Orbital Fibroblasts in Graves’ Orbitopathy
Open access status: An open access version is available from UCL Discovery
DOI: 10.1167/iovs.15-16580
Publisher version: http://dx.doi.org/10.1167/iovs.15-16580
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.
Keywords: Science & technology, life sciences & biomedicine, ophthalmology, mesenchymal stem cells, grave's orbitopathy, orbital fibroblasts, thyroid-associated ophthalmopathy, umbilical-cord blood, human bone-marrow, adipose-tissue, stromal cells, myogenic differentiation, chondrogenic differentiation, dependent mechanism, in-vitro, expression.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Computer Science
URI: https://discovery.ucl.ac.uk/id/eprint/1491800
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