人骨髓间充质干细胞端粒调控机制的研究

发布时间：2018-04-06 00:12

本文选题：间充质干细胞　切入点：端粒酶　出处：《浙江大学》2006年博士论文

【摘要】：间充质干细胞(Mesenchymal stem cells,MSCs)具有高度扩增和自我更新能力及多向分化潜能,它能分化成为成骨细胞、软骨细胞、脂肪细胞、造血支持基质细胞、心肌细胞、神经元细胞与神经胶质细胞。经多次传代培养后MSCs仍保持这种多向分化潜能。MSCs还具有低免疫原性特性。基于MSCs这些特性,MSCs已经被广泛用于干细胞治疗、受损组织修复和基因治疗等临床应用试验研究中。虽然MSCs具有良好的临床应用前景,但其在骨髓内的含量极低,仅占骨髓有核细胞的0.001%到0.01%,难以达到临床有效治疗应用的需要。因此,为了获得足够数量的MSCs,需要进一步在体外进行培养、扩增。文献报道,MSCs至少要经过约10个细胞倍增时间(Populmion Doublings,PDs)扩增才能达到临床有效治疗的细胞数量。但是现有研究显示MSCs在体外扩增能力有限,完成10个PDs培养后MSCs的生命周期的损失将超过50%,严重地影响了MSCs的自我更新、增殖、分化和归巢能力,从而限制了其临床应用。因此,如何提高MSCs的分裂增殖能力、延长其生命周期是目前MSCs生物学特性理论研究和应用研究中亟待解决的问题。端粒是染色体末端由TTAGGG重复序列和相关结合蛋白质组成的特殊保护性结构。端粒的主要功能是防止染色体末端降解、融合、重组及DNA损伤修复系统的异常识别,以维持染色体的完整性和基因组的稳定性。端粒与细胞的
[Abstract]:Mesenchymal stem cells (MSCs) are highly proliferative and self-renewing and have the potential to differentiate into osteoblasts, chondrocytes, adipocytes, hematopoietic support stromal cells, cardiomyocytes, osteoblasts, chondrocytes, adipocytes, hematopoietic support stromal cells and cardiomyocytes.Neurons and glial cells.The multidirectional differentiation potential of MSCs was maintained after multiple passages. MSCs also had low immunogenicity.MSCs has been widely used in stem cell therapy, repair of damaged tissue and gene therapy.Although MSCs has a good prospect of clinical application, its content in bone marrow is very low, which only accounts for 0.001% to 0.01% of the nucleated bone marrow cells, so it is difficult to meet the need of effective clinical treatment.Therefore, in order to obtain sufficient numbers of MSCs, it is necessary to further culture and amplify in vitro.It is reported that MSCs can only be amplified by popululmion Doublings PDs at least 10 cell doubling times in order to reach the number of cells that can be effectively treated clinically.However, existing studies show that the ability of MSCs amplification in vitro is limited, and the life cycle loss of MSCs after completing 10 PDs cultures will exceed 50%, which seriously affects the ability of self-renewal, proliferation, differentiation and homing of MSCs, thus limiting its clinical application.Therefore, how to improve the ability of mitotic proliferation and prolong the life cycle of MSCs is an urgent problem to be solved in the theoretical research and application of MSCs biological characteristics.Telomeres are special protective structures composed of TTAGGG repeats and associated binding proteins at the end of chromosomes.The main function of telomere is to prevent chromosome terminal degradation, fusion, recombination and abnormal recognition of DNA damage repair system in order to maintain chromosome integrity and genome stability.Telomere and cellular
【学位授予单位】：浙江大学
【学位级别】：博士
【学位授予年份】：2006
【分类号】：R329.2

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