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Implantation of human olfactory ecto-mesenchymal stem cells restores locomotion in a rat model of Parkinson's disease
Journal of Chemical Neuroanatomy ( IF 2.8 ) Pub Date : 2021-04-30 , DOI: 10.1016/j.jchemneu.2021.101961
Mohammad Farhadi 1 , Mahdi Eskandarian Boroujeni 2 , Seyed Kamran Kamrava 1 , Zohreh Bagher 1 , Ava Modirzadeh Tehrani 3 , Fakhroddin Aghajanpour 4 , Samira Ezi 4 , Reza Soltani 4 , Aysan Khatmi 4 , Rafieh Alizadeh 1
Affiliation  

One of the complex neurodegenerative disorders is Parkinson disease (PD). PD is mainly caused by dopaminergic (DAergic) neuron degeneration in the midbrain. The loss of DAergic neurons is considered as a key reason of motor functional defects in PD patients. Cell replacement strategies are considered as an alternative remedy to effectively address neurodegeneration in PD. In this report, we evaluated the restorative effect of human olfactory ecto-mesenchymal stem cells (OE-MSCs) in rat models of PD. Accordingly, human OE-MSCs were isolated and phenotypically characterized by flow cytometry and immunocytochemistry. Next, the undifferentiated OE-MSCs were unilaterally transplanted into the striatum of 6-hydroxydopamine (6-OHDA)-lesioned rat models, followed by molecular and histological analyzes as well as assessment of motor skills. Our results displayed that the grafting of OE-MSCs increased the expression of DAergic markers namely dopamine transporter (DAT), tyrosine hydroxylase (TH), nuclear receptor related-1 (Nurr1) in a 6-OHDA model compared with that of control, detected by immunohistochemical staining and western blot. Moreover, noticeable improvements in motor coordination, muscle activity and locomotor performance were observed in 6-OHDA model of PD following OE-MSCs transplantation. Taken together, our finding indicates that undifferentiated OE-MSCs might be counted as an appropriate source for cell replacement therapy particularly aimed at PD.



中文翻译:

植入人类嗅觉外间充质干细胞可恢复帕金森病大鼠模型的运动

复杂的神经退行性疾病之一是帕金森病 (PD)。PD 主要由中脑中的多巴胺能(DAergic)神经元变性引起。DAergic 神经元的丧失被认为是 PD 患者运动功能缺陷的关键原因。细胞替代策略被认为是有效解决 PD 神经退行性变的替代疗法。在本报告中,我们评估了人类嗅觉外间充质干细胞 (OE-MSCs) 在 PD 大鼠模型中的恢复作用。因此,通过流式细胞术和免疫细胞化学分离人类 OE-MSCs 并对其进行表型表征。接下来,将未分化的 OE-MSCs 单侧移植到 6-羟基多巴胺 (6-OHDA) 损伤大鼠模型的纹状体中,然后进行分子和组织学分析以及运动技能评估。我们的结果表明,与对照相比,OE-MSCs 的移植增加了 DAergic 标志物的表达,即多巴胺转运蛋白 (DAT)、酪氨酸羟化酶 (TH)、核受体相关-1 (Nurr1) 在 6-OHDA 模型中的表达。通过免疫组织化学染色和蛋白质印迹。此外,在 OE-MSCs 移植后的 PD 6-OHDA 模型中观察到运动协调、肌肉活动和运动性能的显着改善。总之,我们的发现表明未分化的 OE-MSC 可能被视为特别针对 PD 的细胞替代疗法的合适来源。免疫组化染色和western blot检测。此外,在 OE-MSCs 移植后的 PD 6-OHDA 模型中观察到运动协调、肌肉活动和运动性能的显着改善。总之,我们的发现表明未分化的 OE-MSC 可能被视为特别针对 PD 的细胞替代疗法的合适来源。免疫组化染色和western blot检测。此外,在 OE-MSCs 移植后的 PD 6-OHDA 模型中观察到运动协调、肌肉活动和运动性能的显着改善。总之,我们的发现表明未分化的 OE-MSC 可能被视为特别针对 PD 的细胞替代疗法的合适来源。

更新日期:2021-05-03
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