ATP7B gene therapy of autologous reprogrammed hepatocytes alleviates copper accumulation in a mouse model of Wilson's disease.

ABSTRACT:

Background and aims

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.

Approach and results

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 t

SUBMITTER: Cai H 

PROVIDER: S-EPMC9790736 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature