Silicate fiber scaffold-based 3D perfusion cultures of the human colorectal cancer cell line HT-29 by using a microfluidic chip

Abstract

Three-dimensional (3D) tumor models have been established for more precise drug discovery in vitro. We previously demonstrated an in vitro 3D tumor model using silicate fiber scaffold (SFs) to assess the efficacy of potential anticancer drugs. However, mechanical forces, such as shear stress, which are known to regulate cell behavior in tissues, were absent in the model. In the present study, we developed a novel microfluidic chip that is based on a computational flow simulation. The microfluidic chip was prepared with a 3D computer aided design (CAD)/printer. The human colon adenocarcinoma cell line (HT-29) on SFs formed a mature 3D structure in this perfusion culture system and showed time-dependent drug uptake. In addition, this culture system allowed for control of the intensity of shear stress to the 3D cells by changing the fluid flow. The expression of tumor development-related genes, such as ATP synthase and CXCS4, was induced by fluid flow shear forces. This technology provides a valuable tool for future drug screening and metastasis studies.