Liver organoids cocultured on decellularized native liver scaffolds as a bridging therapy improves survival from liver failure in rabbits

The present study aimed to develop viable liver organoids using decellularized native liver scaffolds and evaluate the efficacy of human liver organoid transplantation in a rabbit model of cirrhosis. Liver organoids were formed by coculture of hepatocyte-like cells derived from the human-induced pluripotent stem cells with three other cell types. Twelve 3-mo-old New Zealand White Rabbits underwent a sham operation, bile duct ligation, or biliary duct ligation followed by liver organoid transplantation. Liver organoid structure and function before and after transplantation were evaluated using histological and molecular analyses. A survival analysis using the Kaplan-Meier method was performed to determine the cumulative probability of survival according to liver organoid transplantation with significantly greater overall survival observed in rabbits that underwent liver organoid transplantation (P = 0.003, log-rank test). The short-term group had higher hepatic expression levels of ALB and CYP3A mRNA and lower expression levels of AST mRNA compared to the long-term group. The short-term group also had lower collagen deposition in liver tissues. Transplantation of human liver organoids cocultured in decellularized native liver scaffold into rabbits that had undergone bile duct ligation improved short-term survival and hepatic function. The results of the present study highlight the potential of liver organoid transplantation as a bridging therapy in liver failure; however, rejection and poor liver organoid function may limit the long-term efficacy of this therapeutic approach.