將人類皮膚細胞轉(zhuǎn)化為誘導(dǎo)多能干細胞需要植入相關(guān)基因,，而這些外來基因有致癌等風(fēng)險。美國科學(xué)家在最新一期《細胞》雜志上發(fā)表研究報告說,，他們在上述轉(zhuǎn)化完成后，首次成功地從所獲得的誘導(dǎo)多能干細胞中移除這些基因,，且保證其基本功能不受影響,。
這項研究是美國白頭生物醫(yī)學(xué)研究所等機構(gòu)的科學(xué)家完成的。他們利用病毒將“c－Myc”等4個基因植入人類皮膚細胞,，將其轉(zhuǎn)化為誘導(dǎo)多能干細胞,。與此同時,，他們使用一種基因編碼技術(shù),，使得在基因序列中，外來基因的兩端留存有特殊標(biāo)志,。轉(zhuǎn)化完成后,，他們再用一種名為“Cre”的酶識別這種標(biāo)志，以此找到外來基因并將其移除,。
外來基因被移除后的誘導(dǎo)多能干細胞仍然具備和其他干細胞類似的基本功能,，但卻避免了“c－Myc”等外來基因可能帶來的癌變風(fēng)險和其他潛在風(fēng)險。
參與此項研究的科學(xué)家魯?shù)婪?middot;耶尼施說,，有研究者曾用老鼠細胞做過類似實驗,，但利用人類細胞成功進行上述試驗在世界上還是首次。
此次研究所用的皮膚細胞來自帕金森氏癥患者,，通過上述方法培育出誘導(dǎo)多能干細胞后,，又成功將其培育成為多巴胺神經(jīng)元細胞，這是帕金森氏癥患者大腦中所缺少的一種細胞,。因此,，相關(guān)成果有望為帕金森氏癥的治療研究帶來福音。（生物谷Bioon.com）
生物谷推薦原始出處：
Cell,6 March 2009 doi:10.1016/j.cell.2009.02.013
Parkinson's Disease Patient-Derived Induced Pluripotent Stem Cells Free of Viral Reprogramming Factors
Frank Soldner1,4,Dirk Hockemeyer1,4,Caroline Beard1,Qing Gao1,George W. Bell1,Elizabeth G. Cook1,Gunnar Hargus3,Alexandra Blak3,Oliver Cooper3,Maisam Mitalipova1,Ole Isacson3andRudolf Jaenisch1,2,,
1 The Whitehead Institute, 9 Cambridge Center, Cambridge, MA 02142, USA
2 Department of Biology, Massachusetts Institute of Technology, 31 Ames Street, Cambridge, MA 02139, USA
3 Udall Parkinson Disease Research Center of Excellence, Center for Neuroredegeneration Research, McLean Hospital/Harvard Medical School, Belmont, MA 02478, USA
Corresponding author
4 These authors contributed equally to this work
Summary
Induced pluripotent stem cells (iPSCs) derived from somatic cells of patients represent a powerful tool for biomedical research and may provide a source for replacement therapies. However, the use of viruses encoding the reprogramming factors represents a major limitation of the current technology since even low vector expression may alter the differentiation potential of the iPSCs or induce malignant transformation. Here, we show that fibroblasts from five patients with idiopathic Parkinson's disease can be efficiently reprogrammed and subsequently differentiated into dopaminergic neurons. Moreover, we derived hiPSCs free of reprogramming factors using Cre-recombinase excisable viruses. Factor-free hiPSCs maintain a pluripotent state and show a global gene expression profile, more closely related to hESCs than to hiPSCs carrying the transgenes. Our results indicate that residual transgene expression in virus-carrying hiPSCs can affect their molecular characteristics and that factor-free hiPSCs therefore represent a more suitable source of cells for modeling of human disease.
