Effect of inflammatory cytokines on major histocompatibility complex expression and differentiation of human neural stem/progenitor cells
Effect of inflammatory cytokines on major histocompatibility complex expression and differentiation of human neural stem/progenitor cells
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DOI：
10.1634/stemcells.2008-0116
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发表时间：
2008-09-01
期刊：
影响因子：
5.2
通讯作者：
Modo, Michel
中科院分区：
文献类型：
--
作者：
Johansson, Saga;Price, Jack;Modo, Michel
为了开发神经干/祖细胞（NSPCs）移植作为神经退行性疾病的成功治疗，需要考虑植入后可能诱导的炎症反应。炎性细胞因子可以上调移植细胞上的主要组织相容性复合体（MHC）表达，从而使它们更容易受到移植排斥。此外，细胞因子还对细胞分化、迁移和增殖具有深远的影响，这可以极大地影响移植的结果。在这里，我们研究了三种炎性细胞因子，干扰素-γ（IFN-γ），肿瘤坏死因子-α（TNF-α），白细胞介素-6（IL-6），从三个不同的物种（人，猴，大鼠）的MHC分子的表达和分化的两个人NSPC线来自纹状体和海马的影响。人和猴IFN-γ以剂量依赖性方式强烈上调两种NSPC系中的MHC表达，而大鼠IFN-γ仅对海马细胞中的MHC表达有影响。此外，TNF-α，而不是IL-6，上调两个NSPC系中的MHC表达。在细胞因子存在下的NSPCs的分化表明，IFN-γ在纹状体NSPC培养物中使神经元产量增加三倍，并且在海马NSPC培养物中使少突胶质细胞的数量增加两倍。此外，TNF-α增强两种细胞系中的胶质细胞生成，而IL-6刺激神经发生。因此，人NSPC细胞系对细胞因子的反应是物种特异性的，并且还取决于NSPCs的起源区域。从动物模型到临床试验的不同细胞系的成功翻译可能会受到本文报道的MHC和分化的物种特异性调节的实质性影响。
To develop transplantation of neural stem/progenitor cells (NSPCs) as a successful treatment of neurodegenerative disorders, the possible induction of an inflammatory response following implantation needs to be taken into consideration. Inflammatory cytokines can upregulate major histocompatibility complex (MHC) expression on transplanted cells, thereby rendering them more susceptible to graft rejection. Furthermore, cytokines also have a profound effect on cell differentiation, migration, and proliferation, which can greatly affect the outcome of transplantation. Here we studied the effect of three inflammatory cytokines, interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6), from three different species ( human, monkey, rat) on expression of MHC molecules and differentiation of two human NSPC lines derived from striatum and hippocampus. Human and monkey IFN-gamma strongly upregulate MHC expression in both NSPC lines in a dose-dependent manner, whereas rat IFN-gamma has an effect on MHC expression only in hippocampal cells. Furthermore, TNF-alpha, but not IL-6, upregulates MHC expression in both NSPC lines. Differentiation of NSPCs in the presence of cytokines showed that IFN-gamma increased the neuronal yield threefold in striatal NSPC cultures and increased the number of oligodendrocytes twofold in hippocampal NSPC cultures. Addition of TNF-alpha enhanced gliogenesis in both cell lines, whereas IL-6 stimulated neurogenesis. Human NSPC lines' response to cytokines is therefore species specific and also dependent on the NSPCs' region of origin. The successful translation of different cell lines from animal models to clinical trials could be substantially influenced by the species-specific regulation of MHC and differentiation as reported here.