用含有NURR1基因的重组共和缺陷腺病毒治疗过表达NURR1的C17.2神经干细胞治疗帕金森病

Qing-Jun Li, Ya-Mei Tang, Jun Liu, Dao-You Zhou, Xiang-Pen Li, Song-Hua Xiao, Dong-Xing Jian, Yi-Gang Xing
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引用次数: 13

摘要

为了研究NURR1基因在帕金森病(PD)中的潜在益处,我们构建了含有NURR1基因的重组共和缺陷腺病毒(Ad-NURR1),并在移植神经干细胞(NSC)中表达。构建Ad-NURR1,通过原位杂交和western blot分析分别鉴定NURR1 mRNA和蛋白的表达。所鉴定的NURR1蛋白可直接或间接诱导NSC向神经元分化。为了确定转染的NSCs的潜在治疗用途,将细胞移植到6-羟多巴胺损伤的大鼠中。分别通过免疫组织化学和定量试验评估移植了带有或不带有Ad-NURR1腺病毒的NSCs的大鼠的组织病理学和行为改变。Ad-NURR1构建体有效表达NURR1蛋白,可直接或间接诱导NSC向神经元分化。在有或没有Ad-NURR1结构的NSCs治疗的大鼠中,可以看到组织病理学和行为改变,尽管在后者的情况下,益处更强。这些结果表明ad - nurr1表达细胞在PD治疗中具有潜在的治疗益处。Ad-NURR1修饰诱导NSC分化,因此代表了PD的潜在治疗方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Treatment of Parkinson disease with C17.2 neural stem cells overexpressing NURR1 with a recombined republic-deficit adenovirus containing the NURR1 gene.

To study the potential benefit of the NURR1 gene in Parkinson's disease (PD), we constructed a recombinant republic-deficit adenovirus containing the NURR1 gene (Ad-NURR1) and expressed it in transplanted neural stem cells (NSC). Ad-NURR1 was constructed, and NURR1 mRNA and protein expression were identified by in situ hybridization and western blot analysis, respectively. The identified NURR1 protein could directly or indirectly induce NSC differentiation into neurons. To identify a potential therapeutic use for the transfected NSCs, cells were transplanted into 6-hydroxydopamine lesioned rats. Histopathological and behavioral alterations were evaluated via immunohistochemistry and the ration test, respectively, in rats transplanted with NSCs with or without the Ad-NURR1 adenovirus. The Ad-NURR1 construct effectively expressed the NURR1 protein, which could directly or indirectly induce NSC differentiation into neurons. Both histopathological and behavioral alterations were seen in rats treated with NSCs with or without the Ad-NURR1 construct, although in the case of the latter, the benefits were more robust. These results suggest a potential therapeutic benefit for Ad-NURR1-expressing cells in the treatment of PD. The Ad-NURR1 modification induced NSC differentiation and therefore represents a potential therapy for PD.

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