Induction of pluripotent stem cells from adult somatic cells by protein-based reprogramming without genetic manipulation
Induction of pluripotent stem cells from adult somatic cells by protein-based reprogramming without genetic manipulation
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DOI：
10.1182/blood-2010-02-269589
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发表时间：
2010-07-22
期刊：
影响因子：
20.3
通讯作者：
Kim, Hyo-Soo
中科院分区：
文献类型：
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作者：
Cho, Hyun-Jai;Lee, Choon-Soo;Kim, Hyo-Soo
体细胞重编程的概念开启了再生医学的新纪元。已定义因子的转导已成功地实现了多能性。然而，在诱导多能干细胞（iPS）的生成过程中，某些因素的遗传操作可能导致致瘤性，这限制了其进一步的应用。我们报道，将胚胎干（ES）细胞衍生的蛋白质单次转移到主要培养的成年小鼠成纤维细胞中，而不是重复转移或长时间暴露于材料中，可以实现完全重编程，达到多能状态，而无需强制表达异位转基因。在此过程中，基因表达和表观遗传状态由体细胞状态转化为es等效状态。我们验证了基于蛋白质的重编程既不是由蛋白质供体ES细胞污染，也不是由供体ES细胞的DNA/RNA污染。蛋白- ips细胞在生物学和功能上与胚胎干细胞非常相似，并在体外分化为3种胚层。此外，蛋白质- ips细胞具有体内分化（分化良好的畸胎瘤形成）和发育（嵌合小鼠和四倍体囊胚互补）的潜力。我们的研究结果为体细胞重编程提供了另一种安全的策略，可用于促进基于多能干细胞的细胞治疗。[血液杂志];2010;116(3):386-395]
The concept of reprogramming of somatic cells has opened a new era in regenerative medicine. Transduction of defined factors has successfully achieved pluripotency. However, during the generation process of induced pluripotent stem (iPS) cells, genetic manipulation of certain factors may cause tumorigenicity, which limits further application. We report that that a single transfer of embryonic stem (ES) cell-derived proteins into primarily cultured adult mouse fibroblasts, rather than repeated transfer or prolonged exposure to materials, can achieve full reprogramming up to the pluripotent state without the forced expression of ectopic transgenes. During the process, gene expression and epigenetic status were converted from somatic to ES-equivalent status. We verified that protein-based reprogramming was neither by the contamination of protein donor ES cell nor by DNA/RNA from donor ES cell. Protein-iPS cells were biologically and functionally very similar to ES cells and differentiated into 3 germ layers in vitro. Furthermore, protein-iPS cells possessed in vivo differentiation (well-differentiated teratoma formation) and development (chimeric mice generation and a tetraploid blastocyst complementation) potentials. Our results provide an alternative and safe strategy for the reprogramming of somatic cells that can be used to facilitate pluripotent stem cell-based cell therapy. (Blood. 2010; 116(3): 386-395)