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ABCB5+ 角膜缘间充质干细胞群体的抗炎和抗(淋)血管生成特性。

Anti-Inflammatory and Anti-(Lymph)angiogenic Properties of an ABCB5+ Limbal Mesenchymal Stem Cell Population.

机构信息

Department of Ophthalmology, Faculty of Medicine, University Hospital Cologne, University of Cologne, 50937 Cologne, Germany.

RHEACELL GmbH & Co. KG, Im Neuenheimer Feld 517, 69120 Heidelberg, Germany.

出版信息

Int J Mol Sci. 2024 Sep 7;25(17):9702. doi: 10.3390/ijms25179702.

Abstract

Corneal transparency and avascularity are essential for vision. The avascular cornea transitions into the vascularized conjunctiva at the limbus. Here, we explore a limbal stromal cell sub-population that expresses ABCB5 and has mesenchymal stem cell characteristics. Human primary corneal stromal cells were enriched for ABCB5 by using FACS sorting. ABCB5+ cells expressed the MSC markers CD90, CD73, and CD105. ABCB5+ but not ABCB5- cells from the same donor displayed evidence of pluripotency with a significantly higher colony-forming efficiency and the ability of trilineage differentiation (osteogenic, adipogenic, and chondrogenic). The ABCB5+ cell secretome demonstrated lower levels of the pro-inflammatory protein MIF (macrophage migration inhibitory factor) as well as of the pro-(lymph)angiogenic growth factors VEGFA and VEGFC, which correlated with reduced proliferation of Jurkat cells co-cultured with ABCB5+ cells and decreased proliferation of blood and lymphatic endothelial cells cultured in ABCB5+ cell-conditioned media. These data support the hypothesis that ABCB5+ limbal stromal cells are a putative MSC population with potential anti-inflammatory and anti-(lymph)angiogenic effects. The therapeutic modulation of ABCB5+ limbal stromal cells may prevent cornea neovascularization and inflammation and, if transplanted to other sites in the body, provide similar protective properties to other tissues.

摘要

角膜透明性和无血管性对于视力至关重要。无血管的角膜在角膜缘处过渡到血管化的结膜。在这里,我们探索了一种表达 ABCB5 并具有间充质干细胞特征的角膜缘基质细胞亚群。我们通过使用 FACS 分选对人原代角膜基质细胞进行 ABCB5 富集。ABCB5+细胞表达 MSC 标志物 CD90、CD73 和 CD105。ABCB5+但不是来自同一供体的 ABCB5-细胞显示出多能性的证据,具有更高的集落形成效率和三系分化(成骨、成脂和成软骨)的能力。ABCB5+细胞的分泌组显示出较低水平的促炎蛋白 MIF(巨噬细胞迁移抑制因子)以及促(淋)血管生成生长因子 VEGFA 和 VEGFC,这与与 ABCB5+细胞共培养的 Jurkat 细胞增殖减少以及在 ABCB5+细胞条件培养基中培养的血液和淋巴内皮细胞增殖减少相关。这些数据支持这样的假设,即 ABCB5+角膜缘基质细胞是一种具有潜在抗炎和抗(淋)血管生成作用的推定 MSC 群体。ABCB5+角膜缘基质细胞的治疗调节可能预防角膜新生血管形成和炎症,如果移植到体内其他部位,可能会为其他组织提供类似的保护特性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/972c/11395824/0d4cb39538cf/ijms-25-09702-g001.jpg

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