Farhadi Mohammad, Boroujeni Mahdi Eskandarian, Kamrava Seyed Kamran, Bagher Zohreh, Tehrani Ava Modirzadeh, Aghajanpour Fakhroddin, Ezi Samira, Soltani Reza, Khatmi Aysan, Alizadeh Rafieh
ENT and Head & Neck Research Center and Department, The Five Senses Health Institute, Hazrat Rasoul Akram Hospital, Iran University of Medical Sciences, Tehran, Iran.
Department of Human Molecular Genetics, Institute of Molecular Biology and Biotechnology, Faculty of Biology, Adam Mickiewicz University, Poznan, Poland.
J Chem Neuroanat. 2021 Jul;114:101961. doi: 10.1016/j.jchemneu.2021.101961. Epub 2021 Apr 30.
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.
帕金森病（PD）是一种复杂的神经退行性疾病。PD主要由中脑多巴胺能（DAergic）神经元变性引起。多巴胺能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神经退行性变的一种替代疗法。在本报告中，我们评估了人嗅外间充质干细胞（OE-MSCs）在PD大鼠模型中的修复作用。因此，通过流式细胞术和免疫细胞化学对人OE-MSCs进行了分离和表型鉴定。接下来，将未分化的OE-MSCs单侧移植到6-羟基多巴胺（6-OHDA）损伤的大鼠模型纹状体中，随后进行分子和组织学分析以及运动技能评估。我们的结果显示，通过免疫组织化学染色和蛋白质印迹检测，与对照组相比，在6-OHDA模型中，OE-MSCs移植增加了多巴胺能标志物即多巴胺转运体（DAT）、酪氨酸羟化酶（TH）、核受体相关因子1（Nurr1）的表达。此外，在OE-MSCs移植后的PD 6-OHDA模型中，观察到运动协调性、肌肉活动和运动能力有明显改善。综上所述，我们的研究结果表明，未分化的OE-MSCs可能被视为细胞替代治疗的合适来源，特别是针对PD的治疗。
