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J Biosci & Bioeng:柔软培养基质或可促进诱导多能性干细胞的产生

来源:生物谷 2014-05-05 08:51

2014年5月5日 讯 /生物谷BIOON/ --将成体细胞转化成为干细胞,再让干细胞成熟分化成为特性类型的细胞是近年来再生医学研究的重点领域,其为研究者开发新型治疗组织损伤修复疗法提供了很大希望;目前研究者已经开发出了可将成体细胞重编程为干细胞的技术,然而这些技术并不完美而且效率并不高,近日,来自日本理化研究所的研究人员通过研究发现,在柔软或者弹性基质上培养的细胞可以增强某些干细胞重编程标记物的表达水平,相关研究刊登于国际杂志Journal of Bioscience and Bioengineering上。

此前研究者发现,柔软的基质可以影响培养细胞更新和繁殖的能力,本文中研究者通过研究检测是否相同的原理也可以应用到增强诱导多能干细胞(iPS)的产量研究上,iPS是一种可以将成熟的成体成纤维细胞利用特殊方法重编程而形成的一类干细胞。

文章中,研究者利用一系列具有不同组分和弹性的凝胶基质检测其对培养小鼠和人类成纤维细胞的效果,结果显示,相比常规的坚硬塑料培养皿生长的细胞来讲,在柔软基质表面生长的细胞中和重编程干细胞相关的基因活性较强,同时研究者还发现培养细胞基质的改变可以明显改变肌动蛋白纤维的量以及分布情况,这就表明肌动蛋白也介导了重编程成体干细胞的过程。

本文的研究结果对于未来开发新型有效的可再生方法来产生多能干细胞非常必要;研究者Higuchi说道,控制培养基质和化学疗法相结合或许可以作为一种新型重编程技术,但其并不涉及基因的转移,也就是利用多能性因子来进行成熟细胞的逆转录病毒感染;当然基因转移一直是重编程诱导型多能干细胞的主要方法,但是如果研究人员发现了新型产生多能干细胞的方法,那么其或许对于临床应用将更加安全可靠。(生物谷Bioon.com)

Culturing of mouse and human cells on soft substrates promote the expression of stem cell markers

Sayaka Higuchi1, Tomonobu M Watanabe1, 2, Keiko Kawauchi3, Taro Ichimura1, Hideaki Fujita1, 2

Substrate elasticity is a potent regulator of the cell state. Soft substrates have been shown to promote the homogeneous self-renewal of mouse embryonic stem cells through the down-regulation of cell-matrix tractions. We therefore investigated whether soft substrates promote the reprogramming of somatic cells into induced pluripotent stem (iPS) cells. After retroviral infection with five factors, Oct3/4, Klf4, Sox2, Lin28 and Nanog, mouse embryonic fibroblasts (MEFs) were cultured on several artificial substrates of varying elasticity and examined for the expression of pluripotency genes. When MEFs were cultured on soft (<0.1 kPa) polyacrylamide gels coated with gelatin, the expressions of Nanog and Oct3/4 genes were higher than in cells cultured on rigid plastic dishes (∼106 kPa). The same result was obtained at higher elasticity (0.5 kPa) for adult human dermal fibroblasts (HDFa). We also examined whether reprogramming could be enhanced on soft substrates without exogenous gene introduction, finding that cells cultured on soft substrates in the presence of chemicals known to promote cell reprogramming exhibited up-regulated stem cell markers. These results suggest that controlling the substrate stiffness can enhance the initiation of cell reprogramming, which may lead to effective and reproducible iPS cell production.

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