Mesenchymal stem cells from human umbilical cord regulate the expression of major histocompatibility complex in human neural stem cells and their lineages
Mesenchymal stem cells from human umbilical cord regulate the expression of major histocompatibility complex in human neural stem cells and their lineages
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人脐带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
DOI：
10.1016/j.neulet.2020.135359
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发表时间：
2020-09
影响因子：
2.5
通讯作者：
Tingyu Qu
中科院分区：
文献类型：
--
作者：
Hongna Yang;Feng Wang;Xiaodun Liu;Hao Wang;Tingyu Qu
来源于胚胎组织和流产胎脑的人神经干细胞（human neural stem cells，hNSCs）被认为是治疗神经退行性疾病和其他中枢神经系统疾病的最有希望的候选细胞。然而，最常见的问题是免疫排斥，这限制了这些同种异体hNSC疗法的成功使用。来自人脐带的间充质干细胞（Mesenchymal stem cells，MSC）（hUC-MSC）因其免疫调节特性而受到越来越多的关注。在本研究中，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hNSCs和星形胶质细胞表达MHCI（主要组织相容性复合物I类），而神经元在没有IFNγ的情况下几乎不表达MHCI（<5%）。此外，hNSC和神经元均不表达MHCII，而星形胶质细胞的亚群（约18%）在没有IFNγ刺激的情况下表达MHCII。而IFNγ的加入可显著增加hNSCs和星形胶质细胞MHCII的表达。IFNγ对hNSCs和星形胶质细胞MHCI的表达无影响。然后，我们研究了hUC-MSCs是否具有调节hNSCs及其共培养系统中的谱系的免疫原性的能力。我们发现hUC-MSCs不影响hNSCs及其谱系上MHCI的表达，然而，这些细胞能够显著抑制IFNγ诱导的hNSCs和星形胶质细胞上MHCI的上调（p < 0.001）。因此，我们的研究结果表明，hUC-MSCs可能作为潜在的有用的调节剂，以降低同种异体hNSCs的免疫原性在临床应用中。
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.
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影响因子：
3.7
作者：
M. Skardelly;Anja Glien;Claudia Groba;N. Schlichting;M. Kamprad;J. Meixensberger;J. Milošević
通讯作者：
M. Skardelly;Anja Glien;Claudia Groba;N. Schlichting;M. Kamprad;J. Meixensberger;J. Milošević
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影响因子：
16.6
作者：
Morizane A;Kikuchi T;Hayashi T;Mizuma H;Takara S;Doi H;Mawatari A;Glasser MF;Shiina T;Ishigaki H;Itoh Y;Okita K;Yamasaki E;Doi D;Onoe H;Ogasawara K;Yamanaka S;Takahashi J
通讯作者：
Takahashi J
影响因子：
4.6
作者：
Vagaska B;New SE;Alvarez-Gonzalez C;D'Acquisto F;Gomez SG;Bulstrode NW;Madrigal A;Ferretti P
通讯作者：
Ferretti P
影响因子：
5.2
作者：
Weinger, Jason G.;Weist, Brian M.;Plaisted, Warren C.;Klaus, Suzi M.;Walsh, Craig M.;Lane, Thomas E.
通讯作者：
Lane, Thomas E.
影响因子：
3.7
作者：
Yang H;Yang H;Xie Z;Wei L;Bi J
通讯作者：
Bi J