间充质干细胞向神经细胞分化的Tau蛋白表达

发布时间：2019-03-08 15:06

【摘要】：背景与目的骨髓来源的间充质干细胞(Mesenchymal stem cells,MSCs)是存在于骨髓中除造血干细胞(hemopoietic stem cells,HSCs)外的另一种干细胞,是中胚层发育的早期细胞。不仅参与生成造血微环境支持造血,在适宜的条件下还可分化为中胚层和神经外胚层来源的组织细胞:成骨细胞、脂肪细胞、神经细胞、肝细胞、内皮细胞等。因其具有高度自我更新能力和多向分化潜能等优点,是细胞替代治疗、基因治疗理想的细胞来源。现在MSCs的研究热点是寻找高度特异性的分离纯化方法、移植治疗各系统功能障碍并重建组织功能、端粒酶活性的研究、基因治疗的靶细胞,以及与MAPCs的比较研究等;对于MSCs诱导分化为神经细胞的研究,也多停留于神经细胞特异性标记的检测和MSCs动物模型移植后行为学评定等。 Tau蛋白,是一种含量最高的神经元微管相关蛋白(microtubule associated protein,MAPs)。正常情况下,Tau广泛存在于神经元的轴突中。Tau蛋白的主要功能在于促进微管的形成和保持微管的稳定性,降低微管蛋白的解离,并诱导微管成束。Tau蛋白还在神经元的分化、成熟、内分泌活性、受体活化过程中都起着重要的作用。Tau蛋白可以通过它的磷酸化状态从时间和空间上调节微管的组装;Tau蛋白的异常磷酸化可使神经细胞发生功能紊乱而丧失正常生理功能,导致神经系统疾病的发生(如阿尔茨海默病等)。 MSCs的准确诱导分化是其应用于临床治疗的基础,这需要对MSCs发育有关的信号调节、微环境影响作用进行深入地研究。目前研究发现,在体外MSCs
[Abstract]:Background & objective Bone marrow derived mesenchymal stem cells (Mesenchymal stem cells,MSCs) are another kind of stem cells which exist in bone marrow except hematopoietic stem cells (hemopoietic stem cells,HSCs). They are early cells of mesoderm development. It is not only involved in the production of hematopoietic microenvironment to support hematopoiesis, but also can differentiate into mesoderm and neuroectodermal tissue cells: osteoblasts, adipocytes, nerve cells, hepatocytes, endothelial cells and so on. Because of its high self-renewal ability and multi-directional differentiation potential, it is an ideal cell source for cell replacement therapy and gene therapy. At present, the research focus of MSCs is to find highly specific methods of isolation and purification, transplantation to treat dysfunction of various systems and reconstruction of tissue function, research on telomerase activity, target cells for gene therapy, and comparative study with MAPCs, and so on. For the study of MSCs-induced differentiation into nerve cells, the detection of neuron-specific markers and the assessment of behavior after transplantation of MSCs animal model are more important. Tau protein, is the highest content of neuronal microtubule-associated protein (microtubule associated protein,MAPs). The main function of Tau protein is to promote the formation of microtubule and maintain the stability of microtubule, reduce the dissociation of microtubule protein, and induce microtubule bundle formation. Tau protein is still in the differentiation of neurons, and the main function of tau protein is to promote the formation of microtubule and maintain the stability of microtubule. Tau protein plays an important role in the process of maturation endocrine activity and receptor activation. Tau protein can regulate the assembly of microtubule in time and space through its phosphorylation state. Abnormal phosphorylation of Tau protein can cause dysfunction of neural cells and loss of normal physiological function, leading to the occurrence of nervous system diseases (such as Alzheimer's disease). The accurate induction and differentiation of MSCs is the basis of its application in clinical treatment, which requires in-depth study on the signal regulation and microenvironmental effects of MSCs development. At present, it has been found that in vitro MSCs
【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2005
【分类号】：R329

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