骨髓间充质干细胞诱导分化和心肌内移植的实验研究

发布时间：2018-01-30 10:24

本文关键词： 骨髓间充质干细胞阿扎胞苷诱导心肌细胞分化骨髓间充质干细胞分化血管生成凋亡调控　出处：《山东大学》2006年博士论文　论文类型：学位论文

【摘要】：背景骨髓间充质干细胞是一类可进行自我复制和更新的细胞，在一定条件下能够跨胚层向骨、软骨、脂肪、神经、肌肉等多种谱系分化。多项研究证明，间充质干细胞移植入缺血心脏后可以分化形成新生心肌细胞、血管内皮细胞和神经细胞等，还可通过分泌多种生长因子，促进微循环建立，增加血液灌注，提高梗死后心脏功能。将间充质干细胞的多向分化特性应用于临床治疗，可能为心肌梗死后的慢性心力衰竭患者带来新希望。间充质干细胞可在体外培养中被诱导分化为心肌样细胞，具备心肌细胞的部分表型，表达心肌特异物质，甚至产生自发跳动。但是有关人间充质干细胞在体外诱导分化为心肌样细胞的实验较少，诱导后的干细胞在形态学、组织学以及分子生物学方面会有何种改变尚缺乏相关实验证据。干细胞分化是外界刺激和细胞内特异性信号转录调控的共同作用结果。研究发现，成体干细胞分化为心肌样细胞的过程类似胚胎时期的表现，某些心肌发育调控基因在这一过程中再次被激活，但其表达规律如何尚未被阐明。Cripto-1是胚胎心肌发育时期不可缺少的调控因子，，但在成体干细胞分化中是否表达尚无相关研究报道。结合现有的研究进展，我们希望通过诱导纯化人骨髓间充质干细胞分化为心肌样细胞的实验，试图在以下几方面有所发现：(1) 5-氮胞苷能否诱导人间充质干细胞分化为心肌样细胞?(2) 在诱导后不同时间点，细胞的形态、超微结构以及心肌标志物的表达有何差异?(3) Cripto-1是否也作为调控因子参与成体干细胞的分化?希望通过上述问题的研究为阐明干细胞的分化现象和
[Abstract]:Background Bone marrow mesenchymal stem cells (BMSCs) are a kind of cells that can replicate and renew themselves. Under certain conditions, they can differentiate into bone, cartilage, fat, nerve, muscle and other lineages. Mesenchymal stem cells transplanted into the ischemic heart can differentiate into neonatal cardiomyocytes, vascular endothelial cells and nerve cells, but also through the secretion of a variety of growth factors, promote the establishment of microcirculation, increase blood perfusion. The multidirectional differentiation of mesenchymal stem cells in clinical treatment may bring new hope to patients with chronic heart failure after myocardial infarction. Mesenchymal stem cells can be induced to differentiate into cardiomyocyte-like cells in vitro. But there are few experiments on inducing human mesenchymal stem cells to differentiate into cardiomyocyte-like cells in vitro, and the induced stem cells are in morphology. There is no experimental evidence for changes in histology and molecular biology. Stem cell differentiation is the result of external stimulation and transcriptional regulation of intracellular specific signals. It has been found that adult stem cells differentiate into cardiomyocyte-like cells similar to embryonic manifestations. Some regulatory genes of myocardial development were reactivated during this process, but the expression of some genes was not elucidated. Cripto-1 is an indispensable regulatory factor during the development of embryonic myocardium. However, there is no related research report on the expression of human bone marrow mesenchymal stem cells in the differentiation of adult stem cells. Combined with the existing research progress, we hope to induce and purify human bone marrow mesenchymal stem cells to differentiate into cardiomyocyte-like cells. We try to find out whether 5-azacytidine can induce human mesenchymal stem cells to differentiate into cardiomyocyte-like cells. 2) what are the differences in cell morphology, ultrastructure and expression of myocardial markers at different time points after induction? Is Cripto-1 also involved in the differentiation of adult stem cells as a regulatory factor? It is hoped that, through the above research, the differentiation of stem cells and the differentiation of stem cells will be clarified.
【学位授予单位】：山东大学
【学位级别】：博士
【学位授予年份】：2006
【分类号】：R329.2

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