SUPPLIVER: Bioartificial supply for liver failure

Abstract

1) ObjectivesThe SUPPLIVER project aims at developing a liver supply system based on cell encapsulation in alginate beads.2) Material and methodsAfter hepatic cells and alginate were mixed, beads were produced by an extrusion method that made the droplets fall in a gelation bath. A bioreactor was designed to host the beads under a fluidized bed perfusion regimen. The biological components were inserted in a complete and safe extracorporeal circuit based on a therapeutic plasmapheresis device. In vitro trials were performed to assess biological functions and both ex vivo and preliminary in vivo studies focused on the system's safety.3) ResultsThe encapsulation and fluidization processes were validated, showing the maintenance of hepatic functions once spheroids of hepatocytes were formed before encapsulation. The whole extracorporeal circuit was built, including all the monitoring processes for priming and treatment. The first preclinical trials were successful on a sheep model.4) ConclusionThe multidisciplinary consortium succeeded in demonstrating the feasibility of the proposed integrated approach, from cell collection to extracorporeal circuit functions. It led to a promising combined advanced therapies medicinal product, that still needs to be challenged in a large model of hepatic failure.