Simorgh Sara, Bagher Zohreh, Farhadi Mohammad, Kamrava Seyed Kamran, Boroujeni Mahdi Eskandarian, Namjoo Zeinab, Hour Farshid Qiyami, Moradi Salah, Alizadeh Rafieh
Department of Tissue Engineering and Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran.
ENT and Head and Neck Research Center and Department, Hazrat Rasoul Akram Hospital, The Five Senses Health Institute, Iran University of Medical Sciences, Tehran, Iran.
Mol Neurobiol. 2021 Aug;58(8):3835-3847. doi: 10.1007/s12035-021-02392-z. Epub 2021 Apr 15.
Among the various therapeutic procedures used for improving PD, stem cell-based therapy has been shown to be a promising method. Olfactory ectomesenchymal stem cells (OE-MSCs) are a great source of stem cells for PD. Also, the intranasal administration (INA) of stem cells to the neural lesion has several advantages over the other approaches to cellular injections. However, improving the efficacy of INA to produce the highest number of cells at the lesion site has always been a controversial issue. For this purpose, this study was designed to apply the magnetically targeted cell delivery (MTCD) approach to OE-MSCs in the injured striatum area through the IN route in order to explore their outcomes in rat models of PD. Animals were randomly classified into four groups including control, PD model, treatment-NTC (treated with INA of non-target cells), and treatment-TC (treated with INA of target cells). The Alg-SPIONs-labeled OE-MSCs were stained successfully using the Prussian blue method with an intracellular iron concentration of 2.73 pg/cell. It was able to reduce signal intensity in the striatum region by increasing the number of these cells, as shown by the magnetic resonance imaging (MRI). Behavioral evaluation revealed that the administration of OE-MSCs with this novel advanced stem cell therapy alleviated Parkinson's motor dysfunction. Further, histological evaluations confirmed the functional enhancement of dopaminergic neuron cells by the expression of Nurr1, Dopamine transporter (DAT), and paired-like homeodomain transcription factor 3 (TH). Overall, this study showed that INA of OE-MSCs in the MTCD approach enhanced stem cells' therapeutic effects in PD models.
在用于改善帕金森病（PD）的各种治疗方法中，基于干细胞的疗法已被证明是一种很有前景的方法。嗅鞘膜间充质干细胞（OE-MSCs）是用于PD治疗的重要干细胞来源。此外，通过鼻内给药（INA）将干细胞输送到神经损伤部位比其他细胞注射方法具有多个优势。然而，提高INA的疗效以在损伤部位产生最多数量的细胞一直是一个有争议的问题。为此，本研究旨在通过鼻内途径将磁靶向细胞递送（MTCD）方法应用于损伤纹状体区域的OE-MSCs，以探索其在PD大鼠模型中的效果。动物被随机分为四组，包括对照组、PD模型组、治疗-NTC组（用非靶向细胞的INA治疗）和治疗-TC组（用靶向细胞的INA治疗）。使用普鲁士蓝法成功对Alg-SPIONs标记的OE-MSCs进行染色，细胞内铁浓度为2.73 pg/细胞。如磁共振成像（MRI）所示，它能够通过增加这些细胞的数量来降低纹状体区域的信号强度。行为学评估显示，这种新型先进干细胞疗法给予OE-MSCs可减轻帕金森病的运动功能障碍。此外，组织学评估通过Nurr1、多巴胺转运体（DAT）和配对样同源域转录因子3（TH）的表达证实了多巴胺能神经元细胞的功能增强。总体而言，本研究表明MTCD方法中OE-MSCs的INA增强了干细胞在PD模型中的治疗效果。
