Fabrication et caractérisation de puces microfluidiques mimant la microarchitecture du foie, vers le « foie sur puce »

Currently, a high number of drug candidates fail to obtain their marketing authorization or are withdrawn afterwards. This is mostly due to their side effects on the liver, which is the main organ responsible for drug metabolism, that have not been detected by animal testing. The pharmaceutical industry therefore needs new preclinical tools, in order to detect, as early as possible, the potential hepatotoxicity of newly developed molecules. Innovative microsystems providing more physiological conditions for cell culture, including flow generation, have been developed worldwide. However, they do not reproduce all the specificities of the liver, and not least the Hering channel, which is the transition area between hepatocytes, producing the bile, and cholangiocytes, draining it inside bile ducts. Thus, the main goal of this thesis was the development of a new microfluidic system mimicking this structure in vitro. The HepaRG cell line and cells derived from human induced pluripotent stem cells were used. This project was a collaboration between d’Alembert Institute at ENS Paris-Saclay (Gif-sur-Yvette), and the UMR-S 1193 INSERM group, at Paul Brousse hospital (Villejuif). We demonstrated that our systems were reproducing certain liver functions and were therefore promising tools for drug toxicity assessment.