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人胚胎干细胞来源的神经干细胞对单核细胞来源树突状细胞分化和功能的抑制作用。

Inhibitory effects of neural stem cells derived from human embryonic stem cells on differentiation and function of monocyte-derived dendritic cells.

机构信息

Institute of Bioengineering and Nanotechnology, National University of Singapore, Singapore.

出版信息

J Neurol Sci. 2013 Jul 15;330(1-2):85-93. doi: 10.1016/j.jns.2013.04.014. Epub 2013 May 9.

DOI:10.1016/j.jns.2013.04.014
PMID:23664653
Abstract

Neural stem cells (NSCs) possess immunosuppressive characteristics, but effects of NSCs on human dendritic cells (DCs), the most important antigen presenting cells, are less well studied. We used an in vitro approach to evaluate the effects of human NSCs on differentiation of human blood CD14(+) monocytes into DCs. NSCs derived from H1 human embryonic stem cells (hESC-NSCs) and human ReNcell NSC line, as well as human bone marrow derived mesenchymal stem cells (MSCs), were tested. We observed that in response to treatment with interleukin-4 and granulocyte macrophage colony-stimulating factor CD14(+) monocytes co-cultured with NSCs were able to down-regulate CD14 and up-regulate the differentiation marker CD1a, whereas MSC co-culture strongly inhibited CD1a expression and supported prolonged expression of CD14. A similar difference between NSCs and MSCs was noted when lipopolysaccharides were included to induce maturation of monocyte-derived DCs. However, when effects on the function of derived DCs were investigated, NSCs suppressed the elevation of the DC maturation marker CD83, although not the up-regulation of costimulatory molecules CD80, CD86 and CD40, and impaired the functional capacity of the derived DCs to stimulate alloreactive T cells. We did not observe any obvious difference between hESC-NSCs and ReNcell NSCs in inhibiting DC maturation and function. Our data suggest that although human NSCs are less effective than human MSCs in suppressing monocyte differentiation into DCs, these stem cells can still affect the function of DCs, ultimately regulating specific immune responses.

摘要

神经干细胞(NSCs)具有免疫抑制特性,但对人类树突状细胞(DCs)的影响研究较少,DCs 是最重要的抗原呈递细胞。我们采用体外方法评估了人类 NSCs 对人血 CD14(+)单核细胞向 DC 分化的影响。我们测试了源自 H1 人胚胎干细胞(hESC-NSCs)和 ReNcell NSC 系的 NSCs ,以及人骨髓来源的间充质干细胞(MSCs)。结果显示,与 MSC 共培养相比,与 NSCs 共培养的白细胞介素-4 和粒细胞-巨噬细胞集落刺激因子处理后的 CD14(+)单核细胞能够下调 CD14 并上调分化标志物 CD1a,而 MSC 共培养强烈抑制 CD1a 表达并支持 CD14 的延长表达。当加入脂多糖诱导单核细胞来源的 DC 成熟时,NSCs 和 MSCs 之间也观察到类似的差异。然而,当研究衍生 DC 的功能时,NSCs 抑制了 DC 成熟标志物 CD83 的升高,尽管未上调共刺激分子 CD80、CD86 和 CD40,并损害了衍生 DC 刺激同种反应性 T 细胞的功能能力。我们没有观察到 hESC-NSCs 和 ReNcell NSCs 在抑制 DC 成熟和功能方面有任何明显差异。我们的数据表明,尽管人类 NSCs 在抑制单核细胞向 DC 分化方面不如人类 MSCs 有效,但这些干细胞仍能影响 DC 的功能,最终调节特异性免疫反应。

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