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Orbital Fibroblasts From Graves' Orbitopathy Patients Share Functional and Immunophenotypic Properties With Mesenchymal Stem/Stromal Cells.

Abstract：

PURPOSE: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.

journal_name

Invest Ophthalmol Vis Sci

journal_title

Investigative ophthalmology & visual science

authors

Brandau S,Bruderek K,Hestermann K,Görtz GE,Horstmann M,Mattheis S,Lang S,Eckstein A,Berchner-Pfannschmidt U

doi

10.1167/iovs.15-16610

subject

Has Abstract

pub_date

2015-10-01 00:00:00

pages

6549-57

issue

eissn

0146-0404

issn

1552-5783

pii

2461804

journal_volume

pub_type

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Orbital Fibroblasts From Graves' Orbitopathy Patients Share Functional and Immunophenotypic Properties With Mesenchymal Stem/Stromal Cells.