Yin Xiaofeng, Xu Huamin, Jiang Yunxia, Deng Wenshuai, Wu Zeyu, Xiang Hengwei, Sun Peng, Xie Junxia
Department of Neurosurgery, Affiliated Hospital of Medical College, Qingdao University, Qingdao, China.
Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines: Physiology, Medical College of Qingdao University, Qingdao, China.
PLoS One. 2014 Aug 13;9(8):e105118. doi: 10.1371/journal.pone.0105118. eCollection 2014.
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.
帕司配宁(PSPN)是胶质细胞源性神经营养因子(GDNF)家族配体(GFLs)中的一种神经营养因子,已发现其可促进特定神经元群体的存活。本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-羟基多巴胺(6-OHDA)诱导的帕金森病(PD)大鼠模型中的潜在治疗作用。在此,我们致力于体外分离、纯化、鉴定和扩增MSCs。表达分析显示,大鼠MSCs表达了几种神经标志物蛋白,如巢蛋白、胶质纤维酸性蛋白(GFAP)和S100。与Lv-PSPN-MSCs共培养的MES23.5细胞在体外显示出比对照细胞更少的6-OHDA诱导的细胞死亡。当将Lv-PSPN-MSCs注射到PD大鼠的纹状体中时,我们观察了PD大鼠的存活率、迁移、分化及行为变化。我们发现,与Lv空载体-MSCs相比,Lv-PSPN-MSCs在大鼠脑中显示出更高的存活率。旋转行为显示,接受Lv-PSPN-MSCs的大鼠与其他组相比改善最为显著。高效液相色谱(HPLC)结果显示,接受Lv-PSPN-MSCs的大鼠纹状体中多巴胺(DA)含量与其他组相比最高。总之,我们的结果表明,移植Lv-PSPN-MSCs可在PD大鼠中产生显著的治疗效果。