Institute of Clinical Medicine, Department of Internal Medicine, University of Oulu, P.O. Box 5000, FIN-90014 Oulu, Finland.
Exp Cell Res. 2011 Apr 1;317(6):791-801. doi: 10.1016/j.yexcr.2010.12.010. Epub 2010 Dec 21.
Mesenchymal stem cells (MSCs) are widely used in experimental treatments for various conditions that involve normal tissue regeneration via inflammatory repair. It is known that MSCs can secrete multiple soluble factors and suppress inflammation. Even though the effect of MSCs on inflammation has been extensively studied, the effect of inflammation on MSCs is poorly understood. One of the major cytokines released at the site of inflammation is tumor necrosis factor alpha (TNF-α) which is known to induce MSC invasion and proliferation. Therefore, we wanted to test the effects of TNF-α exposure on MSCs derived from human bone marrow. We found, as expected, that cell proliferation was significantly enhanced during TNF-α exposure. However, according to the cell surface marker analysis, the intensity of several antigens in the minimum criteria panel for MSCs proposed by International Society of Cellular Therapy (ISCT) was decreased dramatically, and in certain cases, the criteria for MSCs were not fulfilled. In addition, TNF-α exposure resulted in a significant but transient increase in human leukocyte antigen and CD54 expression. Additional proteomic analysis by two-dimensional difference gel electrophoresis and mass spectrometry revealed three proteins whose expression levels decreased and 8 proteins whose expression levels increased significantly during TNF-α exposure. The majority of these proteins could be linked to immunosuppressive and signalling pathways. These results strongly support reactive and immunosuppressive activation of MSCs during TNF-α exposure, which might influence MSC differentiation stage and capacity.
间充质干细胞（MSCs）广泛应用于各种涉及通过炎症修复进行正常组织再生的实验性治疗中。已知 MSCs 可以分泌多种可溶性因子并抑制炎症。尽管 MSCs 对炎症的作用已被广泛研究，但炎症对 MSCs 的影响却知之甚少。炎症部位释放的主要细胞因子之一是肿瘤坏死因子-α（TNF-α），它已知可诱导 MSC 浸润和增殖。因此，我们想测试 TNF-α 暴露对源自人骨髓的 MSCs 的影响。正如预期的那样，我们发现细胞增殖在 TNF-α 暴露期间显着增强。然而，根据国际细胞治疗学会（ISCT）提出的 MSC 最小标准面板的表面抗原分析，几个抗原的强度显着降低，在某些情况下，不符合 MSC 的标准。此外，TNF-α 暴露导致人白细胞抗原和 CD54 表达显著增加，但短暂。二维差异凝胶电泳和质谱的额外蛋白质组学分析显示，在 TNF-α 暴露期间，有 3 种蛋白质的表达水平下降，8 种蛋白质的表达水平显着增加。这些蛋白质中的大多数与免疫抑制和信号通路有关。这些结果强烈支持 MSC 在 TNF-α 暴露期间的反应性和免疫抑制激活，这可能影响 MSC 分化阶段和能力。
