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人嗅球源性和嗅黏膜源性神经干细胞向多巴胺能神经元样细胞的分化:两种干细胞来源的比较。

Differentiation of human olfactory system-derived stem cells into dopaminergic neuron-like cells: A comparison between olfactory bulb and mucosa as two sources of stem cells.

机构信息

ENT and Head & Neck Research Center and Department, The Five Senses Institute, Hazrat Rasoul Akram Hospital, Iran University of Medical Sciences, Tehran, Iran.

Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

出版信息

J Cell Biochem. 2019 Dec;120(12):19712-19720. doi: 10.1002/jcb.29277. Epub 2019 Jul 11.

DOI:10.1002/jcb.29277
PMID:31297865
Abstract

Cell transplantation has become a possible therapeutic approach in the treatment of neurodegenerative diseases of the nervous system by replacing lost cells. The current study aimed to make a comparison between the differentiation capacity of the olfactory bulb neural stem cells (OB-NSCs) and olfactory ectomesenchymal stem cells (OE-MSCs) into dopaminergic-like neurons under the inductive effect of transforming growth factor β (TGF-β). After culturing and treating with TGF-β, the differentiation capacities of both types of stem cells into dopaminergic neuron-like cells were evaluated. Quantitative real-time polymerase chain reaction analysis 3 weeks after induction demonstrated that the mRNA expression of the dopaminergic activity markers tyrosine hydroxylase (TH), dopamine transporter (DAT), paired box gene 2 (PAX2), and PAX5 in the neuron-like cells derived from OB-NSCs was significantly higher than those derived from OE-MSCs. These findings were further supported by the immunocytochemistry staining showing that the expression of the tyrosine hydroxylase, DAT, PAX2, and paired like homeodomain 3 seemed to be slightly higher in OB-NSCs compared with OE-MSCs. Despite the lower differentiation capacity of OE-MSCs, other considerations such as a noninvasive and easier harvesting process, faster proliferation attributes, longer life span, autologous transplantability, and also the easier and inexpensive cultural process of the OE-MSCs, cumulatively make these cells the more appropriate alternative in the case of autologous transplantation during the treatment process of neurodegenerative disorders like Parkinson's disease.

摘要

细胞移植通过替代丢失的细胞已成为治疗神经系统退行性疾病的一种可能的治疗方法。本研究旨在比较嗅球神经干细胞(OB-NSCs)和嗅外胚层间充质干细胞(OE-MSCs)在转化生长因子β(TGF-β)的诱导作用下向多巴胺能样神经元分化的能力。在培养和 TGF-β处理后,评估两种类型的干细胞向多巴胺能神经元样细胞分化的能力。诱导后 3 周的实时定量聚合酶链反应分析表明,源自 OB-NSCs 的神经元样细胞中多巴胺能活性标志物酪氨酸羟化酶(TH)、多巴胺转运蛋白(DAT)、配对盒基因 2(PAX2)和 PAX5 的 mRNA 表达明显高于源自 OE-MSCs 的神经元样细胞。免疫细胞化学染色进一步证实了这一点,显示源自 OB-NSCs 的酪氨酸羟化酶、DAT、PAX2 和配对同源框 3 的表达似乎略高于 OE-MSCs。尽管 OE-MSCs 的分化能力较低,但其他考虑因素,如非侵入性和更容易的采集过程、更快的增殖特性、更长的寿命、自体移植能力,以及 OE-MSCs 更简单和廉价的培养过程,使得这些细胞在治疗帕金森病等神经退行性疾病的自体移植过程中成为更合适的选择。

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