nature20121129-7

来自哈佛大学干细胞研究所的研究人员解答了关于干细胞分化效率的一个关键问题,提出了一种新方法,能用于任何提高干细胞分化效率的实验中,并指出这一方法将在再生生物学方面具有广泛的应用。

-2012年11月29日《自然》

中文翻译


【题目】通过器官匹配间充质形成胚胎干细胞来源祖细胞的自我更新

【译文】再生医学的一个目标就是利用干细胞取代那些由于损伤或疾病而损失的细胞,这取决于为研究或移植生产过量的相关细胞。为了达到这一目的,干细胞逐步分化成特异性衍生物已经在一些类型细胞中取得了成功,但主要的问题依旧是从分化的一个阶段到下一个阶段细胞的无效转变。如果特异细胞产量很大的话,那么扩大该过程一些阶段的无分化祖细胞将显得十分必要。利用胰脏细胞系作为胚胎干细胞分化的模型,我们证实了这是一个可以解决的问题。与器官匹配的间充质共培养使无分化祖细胞的分化和自我更新变为可能,并可以获得产生超过100百万倍的人类内胚层细胞,并完全保持了它们的发育潜能。该作用对于间充质细胞和被扩增的祖细胞都是特异的。当在体内被移植时,已被连续在间充质上扩展的祖细胞产生了葡萄糖感受细胞和分泌胰岛素的细胞。理论上,阶段特异性更新信号的识别可以合并入任何程序,以使得由干细胞分化而来的大量细胞得到有效生产,并可能因此在再生生物学中受到广泛应用。

英文原稿


[Title]: Self-renewal of embryonic-stem-cell-derived progenitors by organ-matched mesenchyme

[Authors]:Julie B. Sneddon,1, 2 Malgorzata Borowiak1, 2 & Douglas A. Melton1

[Abstract]One goal of regenerative medicine, to use stem cells to replace cells lost by injury or disease, depends on producing an excess of the relevant cell for study or transplantation. To this end, the stepwise differentiation of stem cells into specialized derivatives has been successful for some cell types, but a major problem remains the inefficient conversion of cells from one stage of differentiation to the next. If specialized cells are to be produced in large numbers it will be necessary to expand progenitor cells, without differentiation, at some steps of the process. Using the pancreatic lineage as a model for embryonic-stem-cell differentiation, we demonstrate that this is a solvable problem. Co-culture with organ-matched mesenchyme permits proliferation and self-renewal of progenitors, without differentiation, and enables an expansion of more than a million-fold for human endodermal cells with full retention of their developmental potential. This effect is specific both to the mesenchymal cell and to the progenitor being amplified. Progenitors that have been serially expanded on mesenchyme give rise to glucose-sensing, insulin-secreting cells when transplanted in vivo. Theoretically, the identification of stage-specific renewal signals can be incorporated into any scheme for the efficient production of large numbers of differentiated cells from stem cells and may therefore have wide application in regenerative biology.

原文地址

http://www.nature.com/nature/journal/v491/n7426/full/nature11463.html

 

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