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間充質(zhì)干細胞向神經(jīng)細胞分化的Tau蛋白表達

發(fā)布時間:2019-03-08 15:06
【摘要】:背景與目的 骨髓來源的間充質(zhì)干細胞(Mesenchymal stem cells,MSCs)是存在于骨髓中除造血干細胞(hemopoietic stem cells,HSCs)外的另一種干細胞,是中胚層發(fā)育的早期細胞。不僅參與生成造血微環(huán)境支持造血,在適宜的條件下還可分化為中胚層和神經(jīng)外胚層來源的組織細胞:成骨細胞、脂肪細胞、神經(jīng)細胞、肝細胞、內(nèi)皮細胞等。因其具有高度自我更新能力和多向分化潛能等優(yōu)點,是細胞替代治療、基因治療理想的細胞來源。 現(xiàn)在MSCs的研究熱點是尋找高度特異性的分離純化方法、移植治療各系統(tǒng)功能障礙并重建組織功能、端粒酶活性的研究、基因治療的靶細胞,以及與MAPCs的比較研究等;對于MSCs誘導分化為神經(jīng)細胞的研究,也多停留于神經(jīng)細胞特異性標記的檢測和MSCs動物模型移植后行為學評定等。 Tau蛋白,是一種含量最高的神經(jīng)元微管相關(guān)蛋白(microtubule associated protein,MAPs)。正常情況下,Tau廣泛存在于神經(jīng)元的軸突中。Tau蛋白的主要功能在于促進微管的形成和保持微管的穩(wěn)定性,降低微管蛋白的解離,并誘導微管成束。Tau蛋白還在神經(jīng)元的分化、成熟、內(nèi)分泌活性、受體活化過程中都起著重要的作用。Tau蛋白可以通過它的磷酸化狀態(tài)從時間和空間上調(diào)節(jié)微管的組裝;Tau蛋白的異常磷酸化可使神經(jīng)細胞發(fā)生功能紊亂而喪失正常生理功能,導致神經(jīng)系統(tǒng)疾病的發(fā)生(如阿爾茨海默病等)。 MSCs的準確誘導分化是其應用于臨床治療的基礎(chǔ),這需要對MSCs發(fā)育有關(guān)的信號調(diào)節(jié)、微環(huán)境影響作用進行深入地研究。目前研究發(fā)現(xiàn),在體外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
【學位授予單位】:鄭州大學
【學位級別】:碩士
【學位授予年份】:2005
【分類號】:R329

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