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The Effect of Lentivirus-Mediated PSPN Genetic Engineering Bone Marrow Mesenchymal Stem Cells on Parkinson’s Disease Rat Model

机译:慢病毒介导的PSPN基因工程骨髓间充质干细胞对帕金森氏病大鼠模型的影响

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摘要

Persephin (PSPN) is one of the neurotrophic factors of the glial cell line-derived neurotrophic factor (GDNF) family ligands (GFLs) which have been found to promote the survival of specific populations of neurons. The aim of this study was to assess the potential therapeutic function of gene-modified mesenchymal stem cells (MSCs)-Lv-PSPN-MSCs in 6-OHDA-induced Parkinson’s disease (PD) rats models. Here, we worked on the isolation, purification, identification and amplification of MSCs in vitro. The expression analysis revealed that several of the neural marker proteins like nestin, GFAP and S100 were expressed by rat MSCs. MES23.5 cells co-cultured with Lv-PSPN-MSCs showed less 6-OHDA induced cell death than control cells in vitro. When Lv-PSPN-MSCs were injected into the striatum of PD rats, we observed the survival rate, migration, differentiation and the behavior change of PD rats. We found that Lv-PSPN-MSCs showed higher survival rate in rat brain compared with Lv-null-MSCs. Rotational behavior showed that rats receiving Lv-PSPN-MSCs showed the most significant improvement compared with those in other groups. HPLC results showed the content of DA in striatum of rats which received Lv-PSPN-MSCs was highest compared with those in other groups. In conclusion, our results suggest that transplantation of Lv-PSPN-MSCs can lead to remarkable therapeutic effects in PD rats.
机译:Persephin(PSPN)是神经胶质细胞系神经营养因子(GDNF)家族配体(GFL)的神经营养因子之一,已发现它们可以促进特定神经元群体的存活。这项研究的目的是评估基因修饰的间充质干细胞(MSCs)-Lv-PSPN-MSCs在6-OHDA诱发的帕金森病(PD)大鼠模型中的潜在治疗功能。在这里,我们致力于体外分离,纯化,鉴定和扩增MSC。表达分析表明,大鼠MSCs表达了几种神经标记蛋白,如巢蛋白,GFAP和S100。与Lv-PSPN-MSC共培养的MES23.5细胞在体外显示出比对照细胞少的6-OHDA诱导的细胞死亡。当将Lv-PSPN-MSCs注射入PD大鼠的纹状体时,我们观察了PD大鼠的存活率,迁移,分化和行为变化。我们发现,与Lv-null-MSCs相比,Lv-PSPN-MSCs在大鼠脑中显示出更高的存活率。旋转行为表明,与其他组相比,接受Lv-PSPN-MSC的大鼠表现出最显着的改善。 HPLC结果显示,与其他组相比,接受Lv-PSPN-MSCs的大鼠纹状体中DA含量最高。总之,我们的结果表明,Lv-PSPN-MSC的移植可以在PD大鼠中产生显着的治疗效果。

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