Tumor-Microenvironment-on-Chip Platform for Assessing Drug Response in 3D Dynamic Culture

Abstract

Microphysiological systems involving microfluidic 3D culture of cancer cells have emerged as a versatile toolkit to study tumor biological problems and evaluate potential treatment strategies. Incorporation of microfluidic technologies in 3D tissue culture offers opportunities for realistic simulation of tumor microenvironment in vitro by facilitating a dynamic culture environment mimicking features of human physiology such as reconstituted ECM, interstitial flow, and gradients of drugs and biomacromolecules. This protocol describes development of 3D microfluidic cell culture based on Tumor-Microenvironment-on-Chip (T-MOC) platform modeling tumor blood and lymphatic capillary vessels and the interstitial space in between. Based on earlier applications of T-MOC for transport characteristics, drug response, and tumor-stroma interactions in mammary carcinoma and pancreatic adenocarcinoma, this protocol provides detailed description of device fabrication, on-chip 3D culture, and drug treatment assays. This protocol can easily be adapted for applications involving other cancer types.

Keywords: 3D cell culture; Collagen gel; Drug response; Dynamic cell culture; Microfluidics; On-chip cell culture; Tumor microenvironment; Tumor microenvironment on chip.