biostudies-literatureCai HNational Natural Science Foundation of China1046-1057https://www.ebi.ac.uk/biostudies/studies/S-EPMC9790736biostudies-literatureUnknown76(4)<h4>Background and aims</h4>Wilson's disease (WD) is a rare hereditary disorder due to ATP7B gene mutation, causing pathologic copper storage mainly in the liver and neurological systems. Hepatocyte transplantation showed therapeutic potential; however, this strategy is often hindered by a shortage of quality donor cells and by allogeneic immune rejection. In this study, we aimed to evaluate the function and efficacy of autologous reprogrammed, ATP7B gene-restored hepatocytes using a mouse model of WD.<h4>Approach and results</h4>Sufficient liver progenitor cells (LPCs) were harvested by reprogramming hepatocytes from ATP7B^-/- mice with small molecules, which exhibited strong proliferation and hepatic differentiation capacity in vitro. After lentivirus-mediated mini ATP7B gene tHepatology (Baltimore, Md.)ATP7B gene therapy of autologous reprogrammed hepatocytes alleviates copper accumulation in a mouse model of Wilson's disease.PMC979073681671103Wang XPCheng XCai HfalseATP7B gene therapy of autologous reprogrammed hepatocytes alleviates copper accumulation in a mouse model of Wilson's disease.<h4>Background and aims</h4>Wilson's disease (WD) is a rare hereditary disorder due to ATP7B gene mutation, causing pathologic copper storage mainly in the liver and neurological systems. Hepatocyte transplantation showed therapeutic potential; however, this strategy is often hindered by a shortage of quality donor cells and by allogeneic immune rejection. In this study, we aimed to evaluate the function and efficacy of autologous reprogrammed, ATP7B gene-restored hepatocytes using a mouse model of WD.<h4>Approach and results</h4>Sufficient liver progenitor cells (LPCs) were harvested by reprogramming hepatocytes from ATP7B^-/- mice with small molecules, which exhibited strong proliferation and hepatic differentiation capacity in vitro. After lentivirus-mediated mini ATP7B gene t2022-01-01T00:00:00Z2022 Oct2026-07-14T16:00:33.148Z2025-04-05T08:47:27.354ZS-EPMC97907363534006110.1002/hep.32484