A three-dimensional biomimetic microfluidic chip to study the behavior of hepatic stellate cell under the tumor microenvironment

In this paper, we designed a three-dimensional cell co-cultured microfluidic chip, which generated inter-stitial flow and oxygen gradient to simulate the complex tumor microenvironment. It consisted of five parallel cell culture channels and one hypoxic channel. These channels were constructed for the culture of mouse liver tumor cells (Hepa1-6), mouse liver stellate cells (JS-1), the simulation of extracellular ma-trix, complex biochemical factors (hypoxia and interstitial flow), and the supply of cellular nutrients. The 3D-interstitial flow-hypoxia model was used to study the behavior of JS-1 cells under the effect of tumor microenvironment (TME). The results showed that by co-cultured with Hepa1-6 cells, hypoxia of Hepa1-6 cells, and adding TGF-beta 1 by interstitial flow, the migration of JS-1 cells could be promoted. Similarly, activated JS-1 cells could led to the epithelial-mesenchymal transformation in co-cultured Hepa1-6 cells, which secreted more TGF-beta 1. (c) 2023 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.

Automated summary

In this study, a three-dimensional cell co-cultured microfluidic chip was designed to simulate the complex tumor microenvironment. The chip consisted of multiple channels for cell culture, simulation of extracellular matrix, and the supply of nutrients and bioactive factors. The results showed that the co-culture of Hepa1-6 cells, hypoxia, and TGF-beta 1 promoted the migration of JS-1 cells. Additionally, activated JS-1 cells induced epithelial-mesenchymal transition in co-cultured Hepa1-6 cells, leading to increased secretion of TGF-beta 1.