Journal
BIOSENSORS & BIOELECTRONICS
Volume 175, Issue -, Pages -Publisher
ELSEVIER ADVANCED TECHNOLOGY
DOI: 10.1016/j.bios.2020.112833
Keywords
Intercellular communications; Microfluidic chips; Cancer-associated fibroblasts; Mesenchymal stem cells
Categories
Funding
- China Scholarship Council [201708140082, 201608140100, 201706170027]
- National Health and Medical Research Council (NHMRC) [GNT1160635]
- ARC Industry Transformational Research Hub Scheme [IH150100028]
- ARC Linkage Infrastructure, Equipment and Facilities (LIEF) Project [LE180100043]
- Australia-China Joint Research Centre for Point-of-Care Testing [ACSRF65827, SQ2017YFGH001190]
- Science and Technology Innovation Commission of Shenzhen [KQTD20170810110913065]
- National Natural Science Foundation of China (NSFC) [61729501, 51720105015]
- Australian Research Council [LE180100043] Funding Source: Australian Research Council
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The study introduces a microfluidic chip for studying unidirectional intercellular communication by controlling the flow of signal molecules. The chip demonstrates signal concentration gradient and 3D cell culture, serving as a useful tool for cell communication studies.
Cell co-culture serves as a standard method to study intercellular communication. However, random diffusion of signal molecules during co-culture may arouse crosstalk among different types of cells and hide directive signal-target responses. Here, a microfluidic chip is proposed to study unidirectional intercellular communication by spatially controlling the flow of the signal molecules. The chip contains two separated chambers connected by two channels where the culture media flows oppositely. A zigzag signal-blocking channel is designed to study the function of a specific signal. The chip is applied to study the unidirectional communication between tumor cells and stmmal cells. It shows that the expression of a-smooth muscle actin (a marker of cancer-associated fibroblast (CAF)) of both MRC-5 fibroblasts and mesenchymal stem cells can be up-regulated only by the secreta from invasive MDA-MB-231 cells, but not from non-invasive MCF-7 cells. The proliferation of the tumor cells can be improved by the stromal cells. Moreover, transforming growth factor beta 1 is found as one of the main factors for CAF transformation via the signal-blocking function. The chip achieves unidirectional cell communication along X-axis, signal concentration gradient along Y-axis and 3D cell culture along Z-axis, which provides a useful tool for cell communication studies.
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