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用于将神经生长因子(NGF)基因转移至成年大鼠脑内的骨间充质干细胞:挽救穹窿海马伞损伤诱导变性的NGFR p75阳性神经元。

Bone mesenchymal stem cells for gene transfer of NGF to the adult rat brain: rescue the NGFR p75 positive neurons from fimbria-fornix lesion-induced degeneration.

作者信息

Leng Shuilong, He Junfeng, Fan Wenguo, Cheng Shaowu, Long Dahong, He Hongwen

机构信息

Department of Oral Anatomy and Physiology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510080, PR China.

出版信息

Neurosci Lett. 2008 Dec 31;448(3):282-7. doi: 10.1016/j.neulet.2008.10.016. Epub 2008 Oct 10.

Abstract

The study was to evaluate the therapeutic benefit of transplanted bone mesenchymal stem cells (BMSCs) transfected never growth factor (NGF) gene and GFP gene (as a reporter gene), in treating the rat with fimbria-fornix lesion. After transduction of NGF gene via recombinant retroviral vectors into the rat BMSCs, BMSCs were therefore transformed into the GFP-NGF positive BMSCs, nearly 100% of BMSCs expressed NGF, and then transplanted into basal forebrain of rat with fimbria-fornix lesion. After 2 weeks post-transplantation, the GFP-NGF positive BMSCs survive and fuse in vivo with astroglia or NGFR p75 positive neurons in the basal forebrain, no evidence of transdifferentiation was observed in this study. The number of NGFR p75 positive neurons in basal forebrain of NGF group was significantly higher than those of the void plasmid group (p < 0.05) or the PBS group (p < 0.01). These results indicate that the GFP-NGF positive BMSCs provide, by way of paracrine, NGF that effectively perform the functions of neuroprotection, which cell fusion may be also contribute to.

摘要

本研究旨在评估转染神经生长因子(NGF)基因和绿色荧光蛋白基因(GFP,作为报告基因)的移植骨髓间充质干细胞(BMSC)对穹窿海马伞损伤大鼠的治疗效果。通过重组逆转录病毒载体将NGF基因转导至大鼠BMSC后,BMSC转变为GFP-NGF阳性BMSC,近100%的BMSC表达NGF,随后将其移植到穹窿海马伞损伤大鼠的基底前脑。移植后2周,GFP-NGF阳性BMSC在体内存活并与基底前脑的星形胶质细胞或NGFR p75阳性神经元融合,本研究未观察到转分化迹象。NGF组基底前脑NGFR p75阳性神经元数量显著高于空质粒组(p < 0.05)或PBS组(p < 0.01)。这些结果表明,GFP-NGF阳性BMSC通过旁分泌提供NGF,有效发挥神经保护功能,细胞融合可能也有贡献。

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