人骨髓间充质干细胞向角膜上皮细胞系的分化能力。
Differentiation Capacity of Human Mesenchymal Stem Cells into Keratocyte Lineage.
机构信息
Stein Eye Institute, University of California Los Angeles, Los Angeles, California, United States.
Eye and Ear Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, United States.
出版信息
Invest Ophthalmol Vis Sci. 2019 Jul 1;60(8):3013-3023. doi: 10.1167/iovs.19-27008.
PURPOSE
Mesenchymal stem cells (MSCs) have been extensively studied for their capacity to enhance wound healing and represent a promising research field for generating cell therapies for corneal scars. In the present study, we investigated MSCs from different tissues and their potential to differentiate toward corneal keratocytes.
METHODS
Adipose-derived stem cells, bone marrow MSCs, umbilical cord stem cells, and corneal stromal stem cells (CSSCs) were characterized by their expression of surface markers CD105, CD90, and CD73, and their multilineage differentiation capacity into adipocytes, osteoblasts, and chondrocytes. MSCs were also evaluated for their potential to differentiate toward keratocytes, and for upregulation of the anti-inflammatory protein TNFα-stimulated gene-6 (TNFAIP6) after simulation by IFN-γ and TNF-α.
RESULTS
Keratocyte lineage induction was achieved in all MSCs as indicated by the upregulated expression of keratocyte markers, including keratocan, lumican, and carbohydrate sulfotransferase. TNFAIP6 response to inflammatory stimulation was observed only in CSSCs; increasing by 3-fold compared with the control (P < 0.05).
CONCLUSIONS
Based on our findings, CSSCs appeared to have the greatest differentiation potential toward the keratocyte lineage and the greatest anti-inflammatory properties in vitro.
目的
间充质干细胞（MSCs）因其促进伤口愈合的能力而得到广泛研究，是用于开发角膜瘢痕细胞治疗的很有前途的研究领域。在本研究中，我们研究了来自不同组织的 MSCs 及其向角膜成纤维细胞分化的潜力。
方法
脂肪来源干细胞、骨髓间充质干细胞、脐带干细胞和角膜基质干细胞（CSSCs）通过其表面标志物 CD105、CD90 和 CD73 的表达以及向脂肪细胞、成骨细胞和软骨细胞的多谱系分化能力进行表征。还评估了 MSCs 向成纤维细胞分化的潜力，以及在 IFN-γ和 TNF-α模拟后抗炎蛋白 TNFα 刺激基因 6（TNFAIP6）的上调。
结果
所有 MSCs 均实现了成纤维细胞谱系诱导，表现为成纤维细胞标志物包括角膜蛋白聚糖、穹窿蛋白和糖胺聚糖转移酶的上调表达。仅在 CSSCs 中观察到 TNFAIP6 对炎症刺激的反应；与对照组相比增加了 3 倍（P < 0.05）。
结论
根据我们的发现，CSSCs 似乎具有向成纤维细胞谱系分化的最大潜力和体外最大的抗炎特性。
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