Mimicking Embedded Vasculature Structure for 3D Cancer on a Chip Approaches through Micromilling.
Mimicking Embedded Vasculature Structure for 3D Cancer on a Chip Approaches through Micromilling.
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DOI：
10.1038/s41598-017-16458-3
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发表时间：
2017-12-01
影响因子：
4.6
通讯作者：
Neumann CA
中科院分区：
文献类型：
--
作者：
Wan L;Skoko J;Yu J;Ozdoganlar OB;LeDuc PR;Neumann CA
细胞感知和响应微环境信号的能力受到其三维（3D）环境的影响，其中包括细胞外基质（ECM）。在3D环境中，血管结构为细胞提供营养和氧气，从而影响细胞反应，如运动。然而，细胞运动性研究的解释通常受到应用方法的限制，例如具有矩形通道横截面形态的2D常规软光刻方法。为了更好地模拟细胞对3D血管供应的反应，我们开发了一种具有微流体通道的芯片上的细胞系统，该微流体通道具有嵌入3D胶原基质内的弯曲横截面，该胶原基质比无机聚合物更接近地模拟解剖脉管系统，从而模拟生理上更相关的3D细胞环境。为了实现这一点，我们构建了灌注的微流体通道，通过将牺牲的圆形明胶血管模板嵌入胶原蛋白中，通过温度控制将其去除。将活动乳腺癌细胞预先接种到胶原基质中，当人工血管系统提供受控的化学刺激时，它们向血管结构迁移。我们相信这种创新的血管3D ECM系统可用于为癌症和其他疾病中存在的多方向趋化运动和趋化性期间的细胞动力学提供新的见解。
The ability for cells to sense and respond to microenvironmental signals is influenced by their three dimensional (3D) surroundings, which includes the extracellular matrix (ECM). In the 3D environment, vascular structures supply cells with nutrients and oxygen thus affecting cell responses such as motility. Interpretation of cell motility studies though is often restricted by the applied approaches such as 2D conventional soft lithography methods that have rectangular channel cross-sectional morphology. To better simulate cell responses to vascular supply in 3D, we developed a cell on a chip system with microfluidic channels with curved cross-sections embedded within a 3D collagen matrix that emulates anatomical vasculature more closely than inorganic polymers, thus to mimic a more physiologically relevant 3D cellular environment. To accomplish this, we constructed perfusable microfluidic channels by embedding sacrificial circular gelatin vascular templates in collagen, which were removed through temperature control. Motile breast cancer cells were pre-seeded into the collagen matrix and when presented with a controlled chemical stimulation from the artificial vasculature, they migrated towards the vasculature structure. We believe this innovative vascular 3D ECM system can be used to provide novel insights into cellular dynamics during multidirectional chemokineses and chemotaxis that exist in cancer and other diseases.
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粘着斑蛋白在三维细胞运动中的独特作用。
影响因子：
21.3
作者：
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