干細胞具有修復患病或受損組織的能力,，在再生醫(yī)學方面擁有巨大前景。他們可顯著提高醫(yī)學治療的效果,，如營養(yǎng)不良情況下的肌肉再生,、治療燒傷患者的皮膚移植以及通過骨髓移植治療白血病。但是,，干細胞的獲取所涉及倫理問題,，一直是科研人員的心病。
瑞士洛桑理工大學生命科學學院院長迪埃.托諾稱,，通過約束一些基因的表達,，體細胞能夠被誘導轉化為多能狀態(tài)。例如,，從血友病患者的毛囊中收集一些細胞,，對其重編程,，以具備胚胎前體的多潛能性；糾正凝血功能障礙的基因突變并對其重新管理,，分化為功能齊全的細胞后代,，以實現(xiàn)基因治愈。
增加癌變的風險,？
近日，日內(nèi)瓦大學生物化學系,、米蘭的歐洲腫瘤研究所和托諾實驗室的合作研究成果發(fā)表在《細胞死亡與分化》(Cell Death and Differentiation)上,，該成果表明重編程細胞的“基因不穩(wěn)定性”，主要表現(xiàn)在細胞轉化為其胚胎狀態(tài)的過程中,，更嚴重的是,，觀察到的基因突變類似于在腫瘤細胞中觀察到的突變。
科學家總結稱,，重編程細胞用于再生醫(yī)學研究,，廣泛前期研究是很有必要的。一個相同的,、可靠的結論是：基因異常以一種依附于重編程過程本身的方式在成倍增加,，這通常是因為致癌基因在作怪。作者認為,，致癌基因有誘導基因產(chǎn)生不穩(wěn)定性的能力,。這些結果強調(diào)了開展進一步研究的必要性。
英文原文：http://www.sciencedaily.com/releases/2011/02/110221071528.htm
中文翻譯：http://www.chinastemcell.org/page/zixun_xwdtlist.aspx?infoid=990
生物谷推薦英文摘要：
Cell Death & Differentiation doi:10.1038/cdd.2011.9
Genomic instability in induced stem cells
C E Pasi, A Dereli-?z, S Negrini, M Friedli, G Fragola, A Lombardo, G Van Houwe, L Naldini, S Casola, G Testa, D Trono, P G Pelicci and T D Halazonetis
The ability to reprogram adult cells into stem cells has raised hopes for novel therapies for many human diseases. Typical stem cell reprogramming protocols involve expression of a small number of genes in differentiated somatic cells with the c-Myc and Klf4 proto-oncogenes typically included in this mix. We have previously shown that expression of oncogenes leads to DNA replication stress and genomic instability, explaining the high frequency of p53 mutations in human cancers. Consequently, we wondered whether stem cell reprogramming also leads to genomic instability. To test this hypothesis, we examined stem cells induced by a variety of protocols. The first protocol, developed specifically for this study, reprogrammed primary mouse mammary cells into mammary stem cells by expressing c-Myc. Two other previously established protocols reprogrammed mouse embryo fibroblasts into induced pluripotent stem cells by expressing either three genes, Oct4, Sox2 and Klf4, or four genes, OSK plus c-Myc. Comparative genomic hybridization analysis of stem cells derived by these protocols revealed the presence of genomic deletions and amplifications, whose signature was suggestive of oncogene-induced DNA replication stress. The genomic aberrations were to a significant degree dependent on c-Myc expression and their presence could explain why p53 inactivation facilitates stem cell reprogramming.
