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Mesenchymal stem cells from human umbilical cord regulate the expression of major histocompatibility complex in human neural stem cells and their lineages.
Neuroscience Letters ( IF 2.5 ) Pub Date : 2020-09-16 , DOI: 10.1016/j.neulet.2020.135359
Hongna Yang 1 , Feng Wang 2 , Xiaodun Liu 3 , Hao Wang 1 , Tingyu Qu 3
Affiliation  

hNSCs (human neural stem cells) derived from embryonic tissue and aborted fetal brains are considered to be the most promising candidates for neurodegenerative and other CNS(central nervous system) diseases. However, the most common problem, which limited successful use of these allogeneic hNSC therapy, is immune rejection. Mesenchymal stem cells (MSCs) from human umbilical cord (hUC-MSCs) are receiving increasing attention for their immune-modulatory properties. In the current studies, we firstly investigated the immunogenecity of hNSCs as well as their lineages in cultures with the presence or absence of interferon gamma (IFNγ), a pro-inflammatory factors. Our data revealed that the majority of hNSCs and astrocytes expressed MHCI (major histocompatibility complex class I) while neurons hardly expressed MHCI (<5%) in the absence of IFNγ. In addition, neither hNSCs nor neurons expressed MHCII while a subpopulation (about 18 %) of astrocytes expressed MHCII without IFNγ stimulation. However, the addition of IFNγ in cultures significantly increased the expressions of MHCII on hNSCs and astrocytes. However, IFNγ did not affect the expression of MHCI on hNSCs and astrocytes. We then investigated whether hUC-MSCs had the capacity of regulating the immunogenecity of hNSCs as well as their lineages in a co-culture system. We found that hUC-MSCs did not affect the expression of MHCI on hNSCs and their lineages, however, these cells were able to significantly inhibit the IFNγ-induced up-regulation of MHCII on hNSCs and astrocytes (p < 0.001). Thus, our results suggest that hUC-MSCs may serve as potentially useful modulators to reduce the immunogenicity of allogeneic hNSCs in clinical application.



中文翻译:

来自人脐带的间充质干细胞调节人神经干细胞及其谱系中主要组织相容性复合物的表达。

源自胚胎组织和胎儿大脑流产的hNSC(人类神经干细胞)被认为是神经退行性疾病和其他CNS(中枢神经系统)疾病的最有希望的候选者。然而,限制这些异基因hNSC疗法成功使用的最普遍的问题是免疫排斥。人脐带间充质干细胞(hUC-MSCs)的免疫调节特性受到越来越多的关注。在当前的研究中,我们首先研究了hNSCs及其谱系在存在或不存在促炎因子干扰素γ(IFNγ)的培养物中的免疫原性。我们的数据显示,大多数hNSC和星形胶质细胞表达MHCI(主要组织相容性复合体I类),而神经元在不存在IFNγ的情况下几乎不表达MHCI(<5%)。此外,hNSC和神经元均未表达MHCII,而亚群(约18%)的星形胶质细胞未受IFNγ刺激而表达MHCII。然而,在培养物中添加IFNγ显着增加了hNSC和星形胶质细胞上MHCII的表达。然而,IFNγ不影响hNSC和星形胶质细胞上MHCI的表达。然后,我们研究了hUC-MSC是否具有调节hNSCs及其谱系在共培养系统中的免疫原性的能力。我们发现hUC-MSCs不会影响hNSCs及其谱系上MHCI的表达,但是,这些细胞能够显着抑制IFNγ诱导的hNSCs和星形胶质细胞上MHCII的上调(p <0.001)。从而,

更新日期:2020-09-16
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