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A three-dimensional biomimetic microfluidic chip to study the behavior of hepatic stellate cell under the tumor microenvironment
Affiliation:1. Shanghai Key Laboratory of Functional Materials Chemistry, School of Chemistry and Molecular Engineering, East China University of Science and Technology, Shanghai 200237, China;2. Engineering Research Centre of Pharmaceutical Process Chemistry, Ministry of Education, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China
Abstract:In this paper, we designed a three-dimensional cell co-cultured microfluidic chip, which generated interstitial 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 matrix, 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-β1 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-β1.
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