西乃山医院Nature公布干细胞突破

　　

生物通报道：来自加拿大西乃山医院（Mount Sinai Hospital），多伦多大学，英国Wellcome Trust基因科学园（Wellcome Trust Genome Campus）等处的研究人员发现了一种获得干细胞的新方法，这将有助于治愈一些致命性的疾病，比如脊髓损伤，黄斑变性（macular degeneration），糖尿病和帕金森症等。这项研究成果公布在《Nature》在线版上。

文章的通讯作者室西乃山医院Samuel Lunenfeld研究院的资深研究员Andras Nagy博士，他表示，“我们希望这些干细胞能作为治疗目前无法治愈的许多疾病和情况的基础”，“这种能获得干细胞的新方法并不需要胚胎作为起点，并且能利用许多种成人组织，比如病患自己的皮肤细胞获得干细胞。”

Nagy博士的这种获得多年干细胞的新方法并不需要扰乱健康基因，主要利用了一种新载体传递特殊基因，重新编程细胞，使之成为干细胞，之前的方法都需要病毒来传递基因，这有可能会导致DNA损伤，而Nagy博士的新方法则不需要病毒，因此克服了干细胞治疗方法的一个重要问题。

西乃山医院Samuel Lunenfeld研究院的主任Jim Woodgett认为，“这项研究朝着干细胞为基础的治疗迈进了一大步，而且也说明Lunenfeld研究院在再生医学方面的领先地位。”

这项研究得到了加拿大干细胞网络和Juvenile糖尿病研究基金（美国）的资助。

Nagy博士1994年加入西乃山医院，在2005年，从捐献胚胎中分离得到了干细胞系，这是加拿大的第一个胚胎干细胞系，Nagy博士论文中的一个关键元素从Keisuke Kaji博士处获得，后者的一项发现也公布在3月1日的Nature杂志上。

（生物通：张迪）

原文摘要：

piggyBac transposition reprograms fibroblasts to induced pluripotent stem cells

Transgenic expression of just four defined transcription factors (c-Myc, Klf4, Oct4 and Sox2) is sufficient to reprogram somatic cells to a pluripotent state1, 2, 3, 4. The resulting induced pluripotent stem (iPS) cells resemble embryonic stem cells in their properties and potential to differentiate into a spectrum of adult cell types. Current reprogramming strategies involve retroviral1, lentiviral5, adenoviral6 and plasmid7 transfection to deliver reprogramming factor transgenes. Although the latter two methods are transient and minimize the potential for insertion mutagenesis, they are currently limited by diminished reprogramming efficiencies. piggyBac (PB) transposition is host-factor independent, and has recently been demonstrated to be functional in various human and mouse cell lines8, 9, 10, 11. The PB transposon/transposase system requires only the inverted terminal repeats flanking a transgene and transient expression of the transposase enzyme to catalyse insertion or excision events12. Here we demonstrate successful and efficient reprogramming of murine and human embryonic fibroblasts using doxycycline-inducible transcription factors delivered by PB transposition13. Stable iPS cells thus generated express characteristic pluripotency markers and succeed in a series of rigorous differentiation assays. By taking advantage of the natural propensity of the PB system for seamless excision12, we show that the individual PB insertions can be removed from established iPS cell lines, providing an invaluable tool for discovery. In addition, we have demonstrated the traceless removal of reprogramming factors joined with viral 2A sequences14 delivered by a single transposon from murine iPS lines. We anticipate that the unique properties of this virus-independent simplification of iPS cell production will accelerate this field further towards full exploration of the reprogramming process and future cell-based therapies.