Yang Hongna, Wang Feng, Liu Xiaodun, Wang Hao, Qu Tingyu
Department of Critical-care Medicine, Qilu Hospital of Shandong University, Shandong University, Jinan, Shandong, 250012, China.
Department of Breast Disease, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, China.
Neurosci Lett. 2020 Nov 1;738:135359. doi: 10.1016/j.neulet.2020.135359. Epub 2020 Sep 16.
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.
源自胚胎组织和流产胎儿大脑的人神经干细胞（hNSCs）被认为是神经退行性疾病和其他中枢神经系统（CNS）疾病最有前景的候选治疗手段。然而，限制这些异体hNSC疗法成功应用的最常见问题是免疫排斥。来自人脐带的间充质干细胞（hUC-MSCs）因其免疫调节特性而受到越来越多的关注。在当前研究中，我们首先研究了hNSCs及其谱系在有或没有促炎因子γ干扰素（IFNγ）存在的培养物中的免疫原性。我们的数据显示，在没有IFNγ的情况下，大多数hNSCs和星形胶质细胞表达主要组织相容性复合体I类分子（MHCI），而神经元几乎不表达MHCI（<5%）。此外，hNSCs和神经元均不表达MHCII，而在没有IFNγ刺激的情况下，一小部分星形胶质细胞（约18%）表达MHCII。然而，在培养物中添加IFNγ显著增加了hNSCs和星形胶质细胞上MHCII的表达。然而，IFNγ并不影响hNSCs和星形胶质细胞上MHCI的表达。然后，我们研究了hUC-MSCs在共培养系统中是否具有调节hNSCs及其谱系免疫原性的能力。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MHCII的上调（p<0.001）。因此，我们的结果表明，hUC-MSCs可能作为潜在有用的调节剂，在临床应用中降低异体hNSCs的免疫原性。
