Implantation of human olfactory ecto-mesenchymal stem cells restores locomotion in a rat model of Parkinson's disease

人类嗅觉外胚层间充质干细胞植入可恢复帕金森病大鼠模型的运动能力

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作者:Mohammad Farhadi, Mahdi Eskandarian Boroujeni, Seyed Kamran Kamrava, Zohreh Bagher, Ava Modirzadeh Tehrani, Fakhroddin Aghajanpour, Samira Ezi, Reza Soltani, Aysan Khatmi, Rafieh Alizadeh

Abstract

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.

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