iPSCs的潜在致瘤性及降低致瘤性方法的研究进展

Progress in the tumorigenic potential of iPSCs and methods to reduce it

摘要:

自从2006年山中伸弥成功地将小鼠皮肤成纤维细胞重编程为诱导性多能干细胞 (Induced pluripotent stem cells, iPSCs)，iPSCs已成为科学家们研究的热点之一。而iPSCs在为基础研究和再生医学提供了无限可能的同时，相关争论焦点也随之产生，如iPSCs有可能导致肿瘤已成为其在临床应用前需要进一步证实、面对和解决的问题。目前已经有相关研究人员对iPSCs是否具有潜在致瘤性进行了探索。研究结果表明，iPSCs基因表达谱与癌细胞基因表达谱具有交集，重编程过程中积累了基因损伤，以及在培养过程中的基因突变都是其致瘤性产生的原因之一。研究人员目前已经找到很多减少iPSCs致瘤性的方法，比如优化促重编程因子、筛选表达载体、筛选细胞株等。文中对iPSCs致瘤可能性的原因和如何消除其致瘤性进行了综述。

Abstract:

Since Yamanaka successfully reprogrammed murine fibroblasts into iPSCs in 2006, iPSCs technology has drawn much attention worldwide. Although iPSCs provides tremendous possibilities for both basic research and regenerative medicine, it has meanwhile potential risks, e.g. tumorigenicity. Scientists, therefore, have made efforts in clarifying the mechanism of the cause for iPSCs tumorigenicity and the way how to reduce the risk. The results of some researches reveal some of tumorigenic factors, e.g. the partial similarity of gene expression profiles between cancer cells and iPSCs, the accumulation of the genetic damages in the course of reprogramming process, and mutation in the cellular culture. As a consequence, numerous methods for reducing iPSCs tumorigenicity have been explored, such as minimized use of the reprogramming factors at the controlled manner, and the selection of the expression vector or parental cells. In this paper, the cause of iPSCs tumorigenicity and the current achievements on preventing iPSCs tumorigenesis are reviewed.