Department of Physiology and Neurophysiology Research Center, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Physiology Research Centre, Kashan University of Medical Sciences, Kashan, Iran.
Mol Biol Rep. 2019 Aug;46(4):4293-4302. doi: 10.1007/s11033-019-04883-8. Epub 2019 May 23.
This study aimed to investigate the therapeutic effects of intranasal administration of human endometrium-derived stem cells (HEDSCs) in the mouse model of Parkinson's disease (PD). Thirty days after intrastriatal injection of 6-OHDA, HEDSCs were administrated intranasally in three doses (10, 5 × 10 and 10 cells µl). During 120 days after stem cell administration, behavioral tests were examined. Then the mice were sacrificed and the fresh section of the substantia nigra pars compacta (SNpc) was used for detection of HEDSCs-GFP labeled by fluorescence microscopy method. In addition, immunohistochemistry was used to assay GFP, human neural Nestin, and tyrosine hydroxylase (TH) markers in the fixed brain tissue at the SNpc. Our data revealed that behavioral parameters were significantly improved after cell therapy. Fluorescence microscopy assay in fresh tissue and GFP analysis in fixed tissue were showed that the HEDSCs-GFP labeled migrated to SNpc. The data from immunohistochemistry revealed that the Nestin as a differential neuronal biomarker was expressed in SNpc. Also, TH as a dopaminergic neuron marker significantly increased after HEDSCs therapy in an optimized dose 5 × 10 cells µl. Our results suggest that intranasal administration of HEDSCs improve the PD symptoms in the mouse model of PD dose-dependent manner as a noninvasive method.
本研究旨在探讨鼻腔内给予人子宫内膜来源的干细胞(HEDSCs)在帕金森病(PD)小鼠模型中的治疗效果。在纹状体注射 6-OHDA 30 天后,通过三种剂量(10、5×10 和 10 个细胞 µl)进行鼻腔内 HEDSCs 给药。在干细胞给药后 120 天内,进行行为测试。然后处死小鼠,使用新鲜的 SNpc 部分进行荧光显微镜法检测 GFP 标记的 HEDSCs-GFP。此外,使用免疫组织化学方法检测固定脑组织中 GFP、人神经巢蛋白和酪氨酸羟化酶(TH)标志物。我们的数据显示,细胞治疗后行为参数显著改善。新鲜组织中的荧光显微镜检测和固定组织中的 GFP 分析表明,HEDSCs-GFP 标记迁移到 SNpc。免疫组织化学数据显示,巢蛋白作为一种差异神经元生物标志物在 SNpc 中表达。此外,作为多巴胺能神经元标志物的 TH 在 HEDSCs 治疗的优化剂量 5×10 个细胞 µl 后显著增加。我们的结果表明,鼻腔内给予 HEDSCs 可以改善 PD 症状,这种方法是一种非侵入性的方法,且具有剂量依赖性。