Patterning microscale extracellular matrices to study endothelial and cancer cell interactions in vitro.

Patterning microscale extracellular matrices to study endothelial and cancer cell interactions in vitro.
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DOI:
10.1039/c2lc40819h
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发表时间:
2012-11-07
期刊:
影响因子:
6.1
通讯作者:
Gerecht S
Gerecht S
中科院分区:
工程技术1区
文献类型:
--
作者:
Dickinson LE;Lütgebaucks C;Lewis DM;Gerecht S

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肿瘤小生境的细胞外基质(ECM)为驻留和迁移的细胞提供支持,并提供影响细胞行为的指导性线索。ECM蛋白纤连蛋白(Fn)能够形成血管网络,而透明质酸(HA)已知有助于乳腺肿瘤的发展。为了概括肿瘤微环境的各个方面,我们开发了用于内皮集落形成细胞(ECFC)和乳腺癌细胞(BCC)的共培养的空间限定的Fn和HA系统。使用HA和Fn的顺序微接触印刷开发了微图案化系统。该方法支持ECFC优先粘附于Fn,但不支持BCC优先粘附于HA。因此,我们开发了一种微结构的类似物,以在纤维蛋白水凝胶中与ECFC相邻的空间上组织承载BCC的HA微模塑水凝胶。这些新颖的小型化系统允许分析调节肿瘤血管生成的空间和时间机制,并可用于模拟健康和患病组织的其他微环境。
The extracellular matrix (ECM) of the tumor niche provides support to residing and migrating cells and presents instructive cues that influence cellular behaviours. The ECM protein fibronectin (Fn) enables vascular network formation, while hyaluronic acid (HA) is known to facilitate breast tumor development. To recapitulate aspects of the tumor microenvironment, we developed systems of spatially defined Fn and HA for the co-culture of endothelial colony forming cells (ECFCs) and breast cancer cells (BCCs). A micropatterned system was developed using sequential microcontact printing of HA and Fn. This approach supported the preferential adhesion of ECFCs to Fn, but did not support the preferential adhesion of BCCs to HA. Thus, we developed a microstructured analog to spatially organize BCC-laden HA micromolded hydrogels adjacent to ECFCs in fibrin hydrogels. These novel, miniaturized systems allow the analysis of the spatial and temporal mechanisms regulating tumor angiogenesis, and can be applied to mimic other microenvironments of healthy and diseased tissues.
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