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首页> 外文OA文献 >Co-Culture of Tumor Spheroids and Fibroblasts in a Collagen Matrix-Incorporated Microfluidic Chip Mimics Reciprocal Activation in Solid Tumor Microenvironment
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Co-Culture of Tumor Spheroids and Fibroblasts in a Collagen Matrix-Incorporated Microfluidic Chip Mimics Reciprocal Activation in Solid Tumor Microenvironment

机译：胶原基质结合微流控芯片中肿瘤球体和成纤维细胞的共培养模拟固体肿瘤微环境中的相互激活

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Multicellular 3D culture and interaction with stromal components are considered essential elements in establishing a ‘more clinically relevant’ tumor model. Matrix-embedded 3D cultures using a microfluidic chip platform can recapitulate the microscale interaction within tumor microenvironments. As a major component of tumor microenvironment, cancer-associated fibroblasts (CAFs) play a role in cancer progression and drug resistance. Here, we present a microfluidic chip-based tumor tissue culture model that integrates 3D tumor spheroids (TSs) with CAF in proximity within a hydrogel scaffold. HT-29 human colorectal carcinoma cells grew into 3D TSs and the growth was stimulated when co-cultured with fibroblasts as shown by 1.5-folds increase of % changes in diameter over 5 days. TS cultured for 6 days showed a reduced expression of Ki-67 along with increased expression of fibronectin when co-cultured with fibroblasts compared to mono-cultured TSs. Fibroblasts were activated under co-culture conditions, as demonstrated by increases in α-SMA expression and migratory activity. When exposed to paclitaxel, a survival advantage was observed in TSs co-cultured with activated fibroblasts. Overall, we demonstrated the reciprocal interaction between TSs and fibroblasts in our 7-channel microfluidic chip. The co-culture of 3D TS-CAF in a collagen matrix-incorporated microfluidic chip may be useful to study the tumor microenvironment and for evaluation of drug screening and evaluation.
机译：多细胞3D培养以及与基质成分的相互作用被认为是建立“更具临床相关性”的肿瘤模型的基本要素。使用微流体芯片平台的基质嵌入3D培养可以概括肿瘤微环境内的微尺度相互作用。作为肿瘤微环境的主要组成部分，与癌症相关的成纤维细胞（CAF）在癌症进展和耐药性中发挥作用。在这里，我们提出了一种基于微流控芯片的肿瘤组织培养模型，该模型将3D肿瘤球体（TSs）与CAF集成在水凝胶支架内。 HT-29人结肠直肠癌细胞生长为3D TSs，与成纤维细胞共培养时，其生长受到刺激，如直径在5天内的变化百分比增加1.5倍所示。与单培养TS相比，与成纤维细胞共培养时，培养6天的TS显示出Ki-67的表达降低以及纤连蛋白的表达增加。成纤维细胞在共培养条件下被激活，如α-SMA表达和迁移活性的增加所证明。当暴露于紫杉醇时，在与活化的成纤维细胞共培养的TS中观察到了生存优势。总体而言，我们在我们的7通道微流控芯片中展示了TS和成纤维细胞之间的相互影响。在掺有胶原蛋白基质的微流控芯片中共培养3D TS-CAF可能对研究肿瘤微环境以及评估药物筛选和评估有用。

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