Enhanced Differentiation of Human Embryonic Stem Cells Toward Definitive Endoderm on Ultrahigh Aspect Ratio Nanopillars
Enhanced Differentiation of Human Embryonic Stem Cells Toward Definitive Endoderm on Ultrahigh Aspect Ratio Nanopillars
复制标题
超高纵横比纳米柱增强人类胚胎干细胞向定形内胚层的分化
DOI：
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发表时间：
2016
期刊：
影响因子：
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通讯作者：
N. Gadegaard
中科院分区：
文献类型：
--
作者：
Camilla Holzmann Rasmussen;P. Reynolds;D. R. Petersen;Mattias Hansson;R. McMeeking;M. Dufva;N. Gadegaard
人类胚胎干细胞的分化作为细胞替代疗法的潜在无限来源被广泛研究，以治疗退行性疾病，如糖尿病。人胚胎干细胞的定向分化主要依赖于可溶性因子。尽管，一些研究强调了物理环境的特性，如基质刚度，会影响细胞的行为。这里展示了大量生产的注塑成型聚碳酸酯纳米柱，其表面机械性能，即刚度，可以通过超高纵横比纳米柱的几何设计来控制（刚度可以降低25.0003）。研究发现，高纳米柱产生更柔软的表面，显著增强了多能人胚胎干细胞对最终内胚层细胞的诱导，与平面对照相比，纯群体的分化更加一致。相比之下，与“硬”柱或对照相比，“软”柱向胰腺内胚层的进一步分化不太成功，这表明在分化的不同阶段有不同的线索。为了配合纳米柱的力学性能，引入了表面剪切模量的概念，通过微或纳米图案化来描述工程弹性表面的特性。这提供了一个框架，据此可以比较这种材料和散装弹性体材料之间。
Differentiation of human embryonic stem cells is widely studied as a potential unlimited source for cell replacement therapy to treat degenerative diseases such as diabetes. The directed differentiation of human embryonic stem cells relies mainly on soluble factors. Although, some studies have highlighted that the properties of the physical environment, such as substrate stiffness, affect cellular behavior. Here, mass‐produced, injection molded polycarbonate nanopillars are presented, where the surface mechanical properties, i.e., stiffness, can be controlled by the geometric design of the ultrahigh aspect ratio nanopillars (stiffness can be reduced by 25.0003). It is found that tall nanopillars, yielding softer surfaces, significantly enhance the induction of definitive endoderm cells from pluripotent human embryonic stem cells, resulting in more consistent differentiation of a pure population compared to planar control. By contrast, further differentiation toward the pancreatic endoderm is less successful on “soft” pillars when compared to “stiff” pillars or control, indicating differential cues during the different stages of differentiation. To accompany the mechanical properties of the nanopillars, the concept of surface shear modulus is introduced to describe the characteristics of engineered elastic surfaces through micro or nanopatterning. This provides a framework whereby comparisons can be drawn between such materials and bulk elastomeric materials.
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影响因子：
17.1
作者：
Chen W;Villa-Diaz LG;Sun Y;Weng S;Kim JK;Lam RH;Han L;Fan R;Krebsbach PH;Fu J
通讯作者：
Fu J
影响因子：
13.3
作者：
Reynolds, Paul M.;Pedersen, Rasmus H.;Gadegaard, Nikolaj
通讯作者：
Gadegaard, Nikolaj
影响因子：
23.9
作者：
Borowiak M;Maehr R;Chen S;Chen AE;Tang W;Fox JL;Schreiber SL;Melton DA
通讯作者：
Melton DA
影响因子：
3.4
作者：
Morgan, Joshua T.;Murphy, Christopher J.;Russell, Paul
通讯作者：
Russell, Paul
影响因子：
41.2
作者：
Murphy, William L.;McDevitt, Todd C.;Engler, Adam J.
通讯作者：
Engler, Adam J.