In response, a new generation of systems has emerged, incorporating cells within bioreactors. These bio-artificial livers (BALs), which are extracorporeal bioreactors filled with hepatocytes, are designed to provide both detoxification and synthetic functions. They aim to bridge patients to transplantation or, ideally, promote recovery without the need for grafts. Nevertheless, restoring liver function alone is not sufficient to control the inflammatory response associated with ALF.

With the increasing discard rate of donor livers observed in the last 10 years and linked to an aging donor population and higher rates of metabolic conditions, the concept of machine perfusion has regained strong interest. Three main concepts have been introduced worldwide. First, normothermic regional perfusion (NRP) is performed directly in the donor after circulatory death (DCD) to assess organ viability before any cold ischaemia. The second strategy, ex situ normothermic machine perfusion (NMP), is applied either during or after liver transport in the recipient center  in order to replace cold storage and preserve function by preventing additional ischaemia. The third perfusion concept is a hypothermic oxygenated perfusion (HOPE), an approach applied  after cold storage, to reintroduce oxygen at cold temperatures. There is evidence that this approach protects mitochondria,  reduces the risk of ischaemia-reperfusion injury (IRI) and reduces complications after liver transplantation. Although these three technologies have improved graft assessment and preservation, utilization rates remain limited. Moreover, current protocols allow perfusion for limited periods (4 to 24 hours). Extending ex-situ perfusion for several days represents a major frontier to enable organ repair and optimization prior to transplantation.

Liver disease remains a major cause of morbidity and mortality worldwide, and although liver transplantation can be lifesaving, the shortage of grafts highlights the urgent need for alternative therapeutic strategies for end-stage liver disease. In this context, Team 1 brings together complementary expertise in the development of human pluripotent stem cell-derived  therapies , Mesenchymal Stromal Cells (MSCs) and their secretome, including extracellular vesicles (EVs),bioengineering technology, and cell plasticity.

The team aims to design and develop innovative tools such as organoids, assembloids, tumoroids, extracorporeal liver systems and ex vivo liver graft repair approaches. These bioengineered systems are evaluated through preclinical and translational models to enhance liver function, promote tissue repair, and prevent liver damage after acute injury. In parallel, a more fundamental research axis is focused on unraveling the mechanisms of liver cell plasticity in various pathological contexts. A dedicated line of investigation  also addresses the role  of EVs as biomarkers and potential therapeutic agents in severe liver diseases and regeneration processes.