细胞外基质中存在 ROCK 抑制剂可支持无饲养层的人类胚胎干细胞和诱导多能干细胞在传代时更未分化的生长。

Presence of a ROCK inhibitor in extracellular matrix supports more undifferentiated growth of feeder-free human embryonic and induced pluripotent stem cells upon passaging.

机构信息

Department of Stem Cells and Developmental Biology, Royan Institute for Stem Cell Biology and Technology, ACECR, P.O. Box 19395-4644, Tehran, Iran.

出版信息

Stem Cell Rev Rep. 2010 Mar;6(1):96-107. doi: 10.1007/s12015-009-9103-z.

Abstract

Optimization and development of better defined culture methods for human embryonic and induced pluripotent stem cells (hESCs and hiPSCs) will provide an invaluable contribution to the field of regenerative medicine. However, one problem is the vulnerability of hESCs and hiPSCs to apoptosis that causes a low plating efficiency upon passaging. Herein, we have developed a novel hESCs and hiPSCs culture technique that uses ROCK inhibitor (ROCKi) Y-27632 (10 microM) in Matrigel-coated dishes in both serum- and feeder-free culture conditions. This increases plating efficiency during enzymatic and mechanical passaging as compared to its presence solely in culture medium. Under these conditions, hESCs (three lines) and hiPSCs (two lines) retain their typical morphology, a stable karyotype, express pluripotency markers and have the potential to differentiate into derivatives of all three germ layers after long-term culture. Real-time RT-PCR analysis of stemness-related integrins (alphaV, alpha6, and beta1) has demonstrated that their expression increases in the presence of ROCKi. Similar plating efficiencies have been obtained in both hESCs and hiPSCs with a lower concentration of Y-27632 (800 nM) and another ROCKi (HA-1077/Fasudil), thus ruling out the non-specific effects of Y-27632. These results show that addition of ROCKi in the extracellular matrix can increase the plating efficiency of hESCs and hiPSCs during passaging of clusters. This is due not only to an anti-apoptotic effect, but also to an increase in the ECM-cells interaction. Therefore, we believe this method will be useful for both current and future applications of these pluripotent stem cells.

摘要

优化和开发更好定义的人类胚胎和诱导多能干细胞(hESCs 和 hiPSCs)的培养方法将为再生医学领域做出宝贵贡献。然而,一个问题是 hESCs 和 hiPSCs 容易凋亡,导致传代时贴壁效率低。在此,我们开发了一种新的 hESCs 和 hiPSCs 培养技术,即在无血清和无饲养层条件下,使用 ROCK 抑制剂(ROCKi)Y-27632(10 μM)在 Matrigel 包被的培养皿中培养。与仅在培养基中存在相比,这可提高酶消化和机械传代时的贴壁效率。在这些条件下,hESCs(三条线)和 hiPSCs(两条线)保持其典型形态、稳定的核型,表达多能性标记物,并具有在长期培养后分化为三个胚层衍生物的潜能。实时 RT-PCR 分析干细胞相关整合素(alphaV、alpha6 和 beta1)的表达表明,在 ROCKi 存在下其表达增加。在 hESCs 和 hiPSCs 中,较低浓度的 Y-27632(800 nM)和另一种 ROCKi(HA-1077/Fasudil)也可获得相似的贴壁效率,从而排除了 Y-27632 的非特异性作用。这些结果表明,在细胞团传代时,在细胞外基质中添加 ROCKi 可以提高 hESCs 和 hiPSCs 的贴壁效率。这不仅归因于抗凋亡作用,还归因于细胞外基质与细胞的相互作用增强。因此,我们认为这种方法将对这些多能干细胞的当前和未来应用都非常有用。

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索