Department of Radiation Oncology, Chang Gung Memorial Hospital, Linkou Branch , Taoyuan 333, Taiwan.
ACS Appl Mater Interfaces. 2017 Apr 19;9(15):13092-13101. doi: 10.1021/acsami.7b03021. Epub 2017 Apr 6.
Studying cellular crosstalk is important for understanding tumor initiation, progression, metastasis, and therapeutic resistance. Moreover, a three-dimensional (3D) cell culture model can provide a more physiologically meaningful culture microenvironment. However, studying cellular crosstalk in a 3D cell culture model involves tedious processing. In this study, a paper/poly(methyl methacrylate) (PMMA) hybrid 3D cell culture microfluidic platform was successfully developed for the study of cellular crosstalk. The platform was a paper substrate with culture microreactors placed on a PMMA substrate with hydrogel-infused channels. Different types of cells were directly seeded and cultured in the microreactors. Aberrant cell proliferation of the affected cells was induced by secretions from transfected cells, and the proliferation ratios were investigated using a colorimetric method. The results showed that the responses of cellular crosstalk were different in different types of cells. Moreover, neutralizing and competitive assays were performed to show the functionality of the platform. Additionally, the triggered signaling pathways of the affected cells were directly analyzed by a subsequent immunoassay. The microfluidic platform provides a simple method for studying cellular crosstalk and the corresponding signaling pathways in a 3D culture model.
研究细胞串扰对于理解肿瘤的发生、进展、转移和治疗耐药性非常重要。此外，三维（3D）细胞培养模型可以提供更具生理意义的培养微环境。然而，在 3D 细胞培养模型中研究细胞串扰涉及繁琐的处理过程。在本研究中，成功开发了一种纸/聚甲基丙烯酸甲酯（PMMA）混合 3D 细胞培养微流控平台，用于研究细胞串扰。该平台是一种纸质基底，在 PMMA 基底上放置有带有水凝胶注入通道的培养微反应器。不同类型的细胞直接在微反应器中接种和培养。转染细胞的分泌物诱导受影响细胞的异常增殖，并通过比色法研究增殖率。结果表明，不同类型的细胞中细胞串扰的反应不同。此外，还进行了中和和竞争测定以显示平台的功能。此外，通过随后的免疫测定直接分析受影响细胞的触发信号通路。该微流控平台提供了一种简单的方法，用于在 3D 培养模型中研究细胞串扰和相应的信号通路。
