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胚胎干细胞由于具有发育上的全能性,被认为是用于移植治疗的最佳来源。然而,由于人的胚胎干细胞直接运用引发免疫排斥以及触及伦理矛盾,人们一直在研发多能干细胞。2006年,多能干细胞的研究有了重大进展。首先,Yamanaka实验室构建用逆转录载体将候选因子导入成纤维细胞,而后检测多能性标志基因的表达。结果发现,四种因子Oct3/4、Sox2、c-Myc以及Klf4的组合产生了表达多能性标志基因才有的抗药性的克隆,意味着细胞获得了多能性。用这种方法筛选的细胞无论在形态和增殖分化能力方面均类似于干细胞,而且表达干细胞标志基因以及在体内外能向三个胚层的细胞类型分化,这种细胞被命名为诱导性多能干细胞(iPS细胞)。进一步,用更严格的筛选基因nanog得到的iPS能够嵌合到生殖系中。而后,运用改进的方法从人的成体成纤维细胞也可以得到iPS细胞。然而,这种方法得到的嵌合体小鼠存在肿瘤形成现象,可能是由于c-Myc逆转录病毒整合到了基因组。通过替代的方法,去掉c-Myc的iPS也能够获得。为了进一步降低肿瘤形成的几率,近来发展了一种不依赖于病毒的方法,用质粒载体作为介质。iPS进一步的研究热点在于安全性以及从更严格的医学角度提高诱导iPS的效率,其分子机理和相关的技术问题也有待解决和克服。
Embryonic stem cells, because of their developmental pluripotency, are considered to be the best source for transplantation therapy. However, due to the direct use of human embryonic stem cells to trigger immune rejection and ethical conflicts, people are constantly developing pluripotent stem cells. In 2006, significant progress has been made in the study of pluripotent stem cells. First, Yamanaka’s lab constructed a retroviral vector to introduce candidate factors into fibroblasts, and then tested for pluripotency marker gene expression. The results showed that the combination of the four factors Oct3 / 4, Sox2, c-Myc and Klf4 produced resistant clones expressing the pluripotency marker gene, implying pluripotency of the cells. Cells screened this way resembled stem cells both in morphological and proliferative differentiation capacity, and expressed stem cell marker genes and differentiated into cell types of three germ layers in vitro and in vivo, which cells were named as induced pluripotent stem cells (iPS cells). Further, iPS obtained with a more stringent selection of gene nanogs can be chimeric into the germ line. Subsequently, iPS cells can also be obtained from human adult fibroblasts using an improved method. However, the chimerism mice obtained by this method showed tumor formation possibly due to the integration of the c-Myc retrovirus into the genome. By an alternative approach, iPS, with c-Myc removed, can also be obtained. In order to further reduce the chances of tumor formation, a virus-independent approach has recently been developed using plasmid vectors as media. Further research hot spots of iPS are safety and improving the efficiency of inducing iPS from a more rigorous medical point of view. Its molecular mechanism and related technical problems have yet to be solved and overcome.