Multiwell capillarity-based microfluidic device for the study of 3D tumour tissue-2D endothelium interactions and drug screening in co-culture models

• Published in: Scientific reports 2017-09, Vol.7 (1), p.11998-15, Article 11998
• Main Authors: Virumbrales-Muñoz, María, Ayuso, José María, Olave, Marta, Monge, Rosa, de Miguel, Diego, Martínez-Lostao, Luis, Le Gac, Séverine, Doblare, Manuel, Ochoa, Ignacio, Fernandez, Luis J.
• Format: Article
• Language: English
• Subjects: 13/106; 13/62; 14/1; 14/34; 14/63; 142/126; 631/67/70; 639/166/985; Apoptosis; Breast cancer; Capillarity; Cell culture; Cell proliferation; Drug delivery; Drug resistance; Drug screening; Endothelium; Humanities and Social Sciences; Microfluidics; multidisciplinary; Nutrients; Oxygen; Pattern formation; Science; Science (multidisciplinary); TRAIL protein; Tumor microenvironment; Tumor necrosis factor; Tumors
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-12049-4

The tumour microenvironment is very complex, and essential in tumour development and drug resistance. The endothelium is critical in the tumour microenvironment: it provides nutrients and oxygen to the tumour and is essential for systemic drug delivery. Therefore, we report a simple, user-friendly microfluidic device for co-culture of a 3D breast tumour model and a 2D endothelium model for cross-talk and drug delivery studies. First, we demonstrated the endothelium was functional, whereas the tumour model exhibited in vivo features, e . g ., oxygen gradients and preferential proliferation of cells with better access to nutrients and oxygen. Next, we observed the endothelium structure lost its integrity in the co-culture. Following this, we evaluated two drug formulations of TRAIL (TNF-related apoptosis inducing ligand): soluble and anchored to a LUV (large unilamellar vesicle). Both diffused through the endothelium, LUV-TRAIL being more efficient in killing tumour cells, showing no effect on the integrity of endothelium. Overall, we have developed a simple capillary force-based microfluidic device for 2D and 3D cell co-cultures. Our device allows high-throughput approaches, patterning different cell types and generating gradients without specialised equipment. We anticipate this microfluidic device will facilitate drug screening in a relevant microenvironment thanks to its simple, effective and user-friendly operation.