期刊
BIOMATERIALS
卷 28, 期 21, 页码 3208-3216出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2007.03.023
关键词
cell patterning; embryonic stem cells; cell signaling; microwells
资金
- NCRR NIH HHS [RR18878, R21 RR018878, R21 RR018878-02] Funding Source: Medline
- NIBIB NIH HHS [R01 EB007278, R01 EB007278-01] Funding Source: Medline
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.
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