PLoS ONE：研究人员有效地将血细胞转化为干细胞

约翰霍普金斯大学科学家已经开发出一种可靠的方法来把血细胞恢复到原始的干细胞状态，一旦获得干细胞样特性后就可以发展成体内任何其他类型的细胞。这项研究工作结果发表在8月8日的PLoS One杂志上，约翰霍普金斯大学细胞工程和Kimmel癌症中心肿瘤科及儿科助理教授Elias Zambidis医学博士、哲学博士说：研究人员能有效地将血细胞转化为干细胞。

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去年春天在<em>PLoS ONE</em>杂志上，Zambidis和他的同事讲述了成功将心脏细胞安全转化成成血细胞的方法。在最新的实验中，他和他的同事们描述将血细胞转化成为所谓的诱导多能干细胞（iPS）的方法。Zambidis说，他的团队已经成功开发一种超级高效、无病毒的方法来制造iPS细胞。一般来说，数百个血细胞中，只有一个或两个可能变成iPS细胞。而使用Zambidis的方法，50％至60％的血细胞将会转变成iPS细胞。

Zambidis的团队还发现，利用病毒将细胞转换成干细胞状态的方法，科学家使用病毒去递送目的基因到细胞中去，以开启转换来自某种类型（例如皮肤或血液）的细胞回到干细胞状态的过程。然而，这种方式使用的病毒会导致基因变异，导致转化后的细胞演变成癌症细胞。为了不使用病毒就将基因插入，Zambidis团队使用了载体质粒。在新的研究中，美国约翰霍普金斯大学研究小组用生长因子处理脐带血细胞，打算用质粒转染四个基因到细胞中。他们用电脉冲刺激细胞，使得该质粒可以通过细胞表面微小的孔已滑动进入细胞内。一旦进入，质粒引发细胞恢复到原始细胞状态。

当科学家比较使用血细胞方法生长的细胞与从毛细胞和皮肤细胞来源的iPS细胞转化成的细胞时，他们发现，最优越的iPS细胞来自只用四种基因改造并与骨髓细胞培养过的造血干细胞。这些细胞在7至14天之内转换为一个原始的干细胞状态。在正在进行的研究中，Zambidis和他的同事正在测试新制造的iPS细胞的质量和转换为其他类型的细胞的能力。生产无病毒iPS细胞的有效方法来可能会加速干细胞疗法的开发。

编译自：<a title="" href="http://medicalxpress.com/news/2012-08-blood-cells-stem-cell-state.html" target="_blank">Researchers return blood cells to stem cell state</a>
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<img src="http://www.bioon.com/biology/UploadFiles/201208/2012082409164372.jpg" alt="" width="115" height="150" border="0" />

<a title="" href="http://dx.doi.org/10.1371/journal.pone.0042838" target="_blank">doi:10.1371/journal.pone.0042838</a>
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<br/><strong>Growth Factor-Activated Stem Cell Circuits and Stromal Signals Cooperatively Accelerate Non-Integrated iPSC Reprogramming of Human Myeloid Progenitors
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Tea Soon Park1,2, Jeffrey S. Huo1,2, Ann Peters1,2, C. Conover Talbot Jr.3, Karan Verma1,2, Ludovic Zimmerlin1,2, Ian M. Kaplan1,2, Elias T. Zambidis1,2* 

Nonviral conversion of skin or blood cells into clinically useful human induced pluripotent stem cells (hiPSC) occurs in only rare fractions (~0.001%–0.5%) of donor cells transfected with non-integrating reprogramming factors. Pluripotency induction of developmentally immature stem-progenitors is generally more efficient than differentiated somatic cell targets. However, the nature of augmented progenitor reprogramming remains obscure, and its potential has not been fully explored for improving the extremely slow pace of non-integrated reprogramming. Here, we report highly optimized four-factor reprogramming of lineage-committed cord blood (CB) myeloid progenitors with bulk efficiencies of ~50% in purified episome-expressing cells. Lineage-committed CD33+CD45+CD34? myeloid cells and not primitive hematopoietic stem-progenitors were the main targets of a rapid and nearly complete non-integrated reprogramming. The efficient conversion of mature myeloid populations into NANOG+TRA-1-81+ hiPSC was mediated by synergies between hematopoietic growth factor (GF), stromal activation signals, and episomal Yamanaka factor expression. Using a modular bioinformatics approach, we demonstrated that efficient myeloid reprogramming correlated not to increased proliferation or endogenous Core factor expressions, but to poised expression of GF-activated transcriptional circuits that commonly regulate plasticity in both hematopoietic progenitors and embryonic stem cells (ESC). Factor-driven conversion of myeloid progenitors to a high-fidelity pluripotent state was further accelerated by soluble and contact-dependent stromal signals that included an implied and unexpected role for Toll receptor-NFκB signaling. These data provide a paradigm for understanding the augmented reprogramming capacity of somatic progenitors, and reveal that efficient induced pluripotency in other cell types may also require extrinsic activation of a molecular framework that commonly regulates self-renewal and differentiation in both hematopoietic progenitors and ESC.

<br/>来源：生物谷

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