Description du sujet de thèse

The liver presents a remarkable regenerative capability, allowing it to restore its mass, structure, and functional stability following tissue injury and cell loss. This regenerative capacity holds great potential in clinical settings, offering promising avenues for treating liver diseases requiring surgical tissue removal and enhancing recovery after surgery. However, the success of liver regeneration varies considerably across patients and conditions, with the process sometimes impaired or failing to initiate, complicating recovery outcomes. Thus, understanding the mechanisms governing liver regeneration is key to improve the survival and long-term health of postoperative patients. Liver regeneration following partial hepatectomy involves intricate signalling pathways, yet the priming factors, especially blood flow-induced mechanical cues, that initiate this process remain poorly understood. Recent advances in microfluidic organ-on-a-chip (OoC) technology offer precise control over critical parameters such as fluid dynamics and mechanical stimuli that closely mimic in vivo conditions. This project aims to develop a vascularized liver−on−a−chip model that closely mimics the microenvironment of the liver, to investigate the roles of flow−dependent mechanical stimuli as early drivers of liver regeneration. The ultimate goal is to establish a robust microphysiological system that supports the ex vivo expansion of patient-derived hepatocytes, advancing regenerative medicine and liver disease treatment.

Contexte de travail

This PhD thesis project will be hosted in the team “Processus dynamiques et multi-échelles de l'organisation spontanée dans la morphogenèse tissulaire” led by Dr. Wenjin Xiao and Prof. Mathieu Hautefeuille, at Laboratory Dev2A (UMR 8263), IBPS, Sorbonne Université. The team possesses expertise in developing application-specific microfluidic models that integrate desired mechanical conditions of fluid flow and substrate viscoelasticity.
The work will be carried out under the direction of Dr. Wenjin Xiao, and under the co-supervision of Dr. Lynda Aoudjehane at ICAN-Human Liver Biology, Hôpital de la Pitié Salpêtrière, Sorbonne Université. The research will be conducted mostly at Dev2A and occasionally at ICAN.

Contraintes et risques

N/A