Cell patterning chip for controlling the stem cell microenvironment
Cell patterning chip for controlling the stem cell microenvironment
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DOI：
10.1016/j.biomaterials.2007.03.023
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发表时间：
2007-07-01
期刊：
影响因子：
14
通讯作者：
Voldman, Joel
中科院分区：
文献类型：
--
作者：
Rosenthal, Adam;Macdonald, Alice;Voldman, Joel
细胞-细胞信号传导是干细胞微环境的重要组成部分，影响分化和自我更新。然而，传统的细胞培养技术不能提供对细胞-细胞相互作用的精确控制，而现有的细胞图案化技术在用于增殖或运动细胞时受到限制。为了解决这些限制，我们创造了生物倒装芯片（BFC），这是一种含有数千个微孔的微加工聚合物芯片，每个微孔的大小都可以捕获单个干细胞。我们已经证明了BFC的功能，通过图案化一个50 × 50网格的小鼠胚胎干细胞（mESC），图案化效率> 75%到各种基板上的细胞培养皿图案与明胶，3-D基板，甚至另一层细胞。我们还使用BFC来图案化细胞的小群体，有和没有细胞-细胞接触，允许接触介导的信号的增量和独立控制。我们提出的定量证据表明，细胞-细胞接触在抑制mESC集落形成中起着重要作用，并表明E-钙粘蛋白参与了这一负调控途径。因此，通过精确控制细胞微环境，我们提供了一种技术，使组织工程和再生医学的新应用。(C)2007-爱思唯尔有限公司保留所有权利。
Cell-cell signaling is an important component of the stem cell microenvironment, affecting both differentiation and self-renewal. However, traditional cell-culture techniques do not provide precise control over cell-cell interactions, while existing cell-patterning technologies are limited when used with proliferating or motile cells. To address these limitations, we created the Bio Flip Chip (BFC), a microfabricated polymer chip containing thousands of microwells, each sized to trap down to a single stem cell. We have demonstrated the functionality of the BFC by patterning a 50 x 50 grid of murine embryonic stem cells (mESCs), with patterning efficiencies > 75% onto a variety of substrates-a cell-culture dish patterned with gelatin, a 3-D substrate, and even another layer of cells. We also used the BFC to pattern small groups of cells, with and without cell-cell contact, allowing incremental and independent control of contact-mediated signaling. We present quantitative evidence that cell-cell contact plays an important role in depressing mESC colony formation, and show that E-cadherin is involved in this negative regulatory pathway. Thus, by allowing exquisite control of the cellular microenvironment, we provide a technology that enables new applications in tissue engineering and regenerative medicine. (C) 2007-Elsevier Ltd. All rights reserved.