格雷夫斯眼眶病患者的眼眶成纤维细胞与间充质干/基质细胞具有相同的功能和免疫表型特征。

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

作者信息

Brandau Sven, Bruderek Kirsten, Hestermann Khaleda, Görtz Gina-Eva, Horstmann Mareike, Mattheis Stefan, Lang Stephan, Eckstein Anja, Berchner-Pfannschmidt Utta

机构信息

Department of Otorhinolaryngology University of Duisburg-Essen, Essen, Germany.

Department of Otorhinolaryngology University of Duisburg-Essen, Essen, Germany 2Department of Ophthalmology, Molecular Ophthalmology Group, University of Duisburg-Essen, Essen, Germany.

出版信息

Invest Ophthalmol Vis Sci. 2015 Oct;56(11):6549-57. doi: 10.1167/iovs.15-16610.

DOI:10.1167/iovs.15-16610

PMID:26457540

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.

摘要

目的

在格雷夫斯眼眶病（GO）中，球后组织的炎症和扩张是一种病理生理过程的结果，在该过程中眼眶成纤维细胞（GO-Fs）被认为是核心细胞类型。然而，在先前的一项研究中，我们观察到GO-Fs表达了一些描述间充质干/基质细胞（MSC）的共有表面标志物。在本研究中，我们通过将GO-Fs与眼眶脂肪来源的间充质干细胞进行比较，进一步阐明其干细胞特征。

方法

我们从GO患者减压手术期间获得的相同球后脂肪活检组织中同时富集原代人GO-MSCs和GO-Fs。按照定义MSC的标准，比较供体匹配的GO-MSCs和-Fs的生物学特性：成纤维细胞样生长、MSC表面标志物谱、多向分化潜能和免疫调节功能。

结果

应用标准化的分离和扩增方案得到了GO-MSCs，其表现出类似成纤维细胞的贴壁形态，增殖并产生透明质酸，与GO-Fs相似。GO-MSCs和GO-Fs均表达眼眶脂肪来源的干细胞表面标志物CD29、CD44、CD71、CD73、CD90、CD105和CD166，体外扩增后CD31、CD34、CD45、CD146和Stro-1呈阴性。此外，GO-MSCs和GO-Fs均表现出脂肪生成、成骨、软骨生成、肌生成和神经分化，尽管GO-Fs的分化能力较低。此外，与GO-MSCs相比，GO-Fs表现出T细胞抑制作用降低，IL-6分泌量减少，提示免疫抑制潜能较低。