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 & Cell Biology, Immunogenetic Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
J Chem Neuroanat. 2019 Mar;96:126-133. doi: 10.1016/j.jchemneu.2019.01.003. Epub 2019 Jan 10.
The generation of dopaminergic neurons from stem cells is a potential therapeutic approach to treat neurodegenerative disorders, such as Parkinson's disease. The current study aims to investigate the potential of two different types of mesenchymal stem cells derived from human Wharton's jelly and nasal cavity for differentiation into dopaminergic neurons. The differentiation capacities of both cell types were evaluated using real-time PCR, immunocytochemistry, flow cytometry and HPLC. Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) are noted for their capability to differentiate into mesodermal and non-mesodermal cells, including neurons. However, it was demonstrated that having the same neuroectodermal origin as the nervous system, the olfactory ectomesenchymal stem cells (OE-MSCs) expressed the neural marker MAP2 as well as dopaminergic markers such as tyrosine hydroxylase (TH), dopamine transporter (DAT) and PITX3 to a greater extent than the WJ-MSCs both at the level of mRNA and protein. Furthermore, quantitative flow cytometric evaluation of these markers at 12 days post-induction supported the above-mentioned results. Finally, the assessment of the functionality of differentiated cells and their ability to synthesize dopamine measured by HPLC revealed that the OE-MSC-derived dopaminergic cells released almost the same amount of dopamine as that secreted by WJ-MSC-derived cells. Thus it showed the difference in their functionality to be negligible. Overall, it may be concluded that higher proliferation and differentiation capacity of OE-MSCs, along with their easier harvestability and autologous transplantability compared with WJ-MSCs, makes them a better cell source for stem cell therapy of neurodegenerative disorders which are caused by degeneration of dopaminergic neurons.
从干细胞产生多巴胺能神经元是治疗神经退行性疾病（如帕金森病）的一种潜在治疗方法。本研究旨在探讨源自人 Wharton 胶和鼻腔的两种不同类型间充质干细胞分化为多巴胺能神经元的潜力。使用实时 PCR、免疫细胞化学、流式细胞术和 HPLC 评估了这两种细胞类型的分化能力。Wharton 胶来源的间充质干细胞（WJ-MSCs）以其分化为中胚层和非中胚层细胞（包括神经元）的能力而闻名。然而，研究表明，具有与神经系统相同的神经外胚层起源的嗅外胚层间充质干细胞（OE-MSCs）表达神经标志物 MAP2 以及多巴胺能标志物，如酪氨酸羟化酶（TH）、多巴胺转运体（DAT）和 PITX3，在 mRNA 和蛋白水平上均比 WJ-MSCs 更为显著。此外，诱导后 12 天对这些标志物的定量流式细胞术评估支持了上述结果。最后，通过 HPLC 评估分化细胞的功能及其合成多巴胺的能力表明，OE-MSC 衍生的多巴胺能细胞释放的多巴胺量与 WJ-MSC 衍生的细胞相似。因此，其功能差异可以忽略不计。总的来说，与 WJ-MSCs 相比，OE-MSCs 具有更高的增殖和分化能力，且易于收获和自体移植，这使其成为神经退行性疾病干细胞治疗的更好细胞来源，这些疾病是由多巴胺能神经元变性引起的。
