Three-dimensional nanofibrillar surfaces promote self-renewal in mouse embryonic stem cells
Three-dimensional nanofibrillar surfaces promote self-renewal in mouse embryonic stem cells
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DOI：
10.1634/stemcells.2005-0170
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发表时间：
2006-02-01
期刊：
影响因子：
5.2
通讯作者：
Meiners, Sally
中科院分区：
文献类型：
--
作者：
Nur-E-Kamal, Alam;Ahmed, Ijaz;Meiners, Sally
小鼠胚胎干细胞（mESC）命运的调控是由促进自我更新或诱导分化的信号网络的相互作用控制的。白血病抑制因子（Leukemia inhibitory factor， LIF）是小鼠干细胞更新所必需的细胞因子，而不是人胚胎干细胞。然而，胚胎成纤维细胞的饲养层能够诱导两种细胞类型的干细胞更新，这表明自我更新信号通路也可能由其他触发因素促进，例如饲养成纤维细胞分泌的替代细胞因子和/或细胞外基质（ECM）的化学或物理特性。我们最近使用了一种合成聚酰胺基质（Ultra-Web），其三维（3D）纳米纤维组织类似于ECM/基底膜。尽管两种系统中都存在LIF，但与没有纳米纤维的组织培养表面相比，mESCs在纳米纤维表面上的生长大大增强了增殖和自我更新。干细胞在纳米纤维表面的增殖和自我更新的增强与小GTPase Rac的激活、磷酸肌肽3激酶（PI3K）途径的激活以及维持多能性所需的同源蛋白Nanog的表达增强相关。PI3K抑制剂可降低纳米纤维表面培养的mESCs中Nanog的表达水平。这些结果支持了培养表面的三维性可能作为激活Rac和PI3K信号通路的线索，从而导致干细胞增殖和自我更新的观点。
The regulation of mouse embryonic stem cell (mESC) fate is controlled by the interplay of signaling networks that either promote self-renewal or induce differentiation. Leukemia inhibitory factor (LIF) is a cytokine that is required for stem cell renewal in mouse but not in human embryonic stem cells. However, feeder layers of embryonic fibroblasts are capable of inducing stem cell renewal in both cell types, suggesting that the self-renewal signaling pathways may also be promoted by other triggers, such as alternative cytokines and/or chemical or physical properties of the extracellular matrix (ECM) secreted by feeder fibroblasts. We have recently used a synthetic polyamide matrix (Ultra-Web) whose three-dimensional (3D) nanofibrillar organization resembles the ECM/basement membrane. Growth of mESCs on this nanofibrillar surface greatly enhanced proliferation and self-renewal in comparison with growth on tissue culture surfaces without nanofibers, despite the presence of LIF in both systems. Enhanced proliferation and self-renewal of the stem cells on nanofibrillar surfaces were correlated with the activation of the small GTPase Rac, the activation of phosphoinositide 3-kinase (PI3K) pathway, and the enhanced expression of Nanog, a homeoprotein required for maintenance of pluripotency. Inhibitors of PI3K reduced the expression level of Nanog in mESCs cultured on 3D nanofibrillar surfaces. These results provide support for the view that the three-dimensionality of the culture surface may function as a cue for the activation of Rac and PI3K signaling pathways, resulting in stem cell proliferation and self-renewal.