Human biliary epithelial cells from discarded donor livers rescue bile duct structure and function in a mouse model of biliary disease

来自废弃供体肝脏的人类胆道上皮细胞在胆道疾病小鼠模型中挽救胆管结构和功能

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作者:John M Hallett, Sofia Ferreira-Gonzalez, Tak Yung Man, Alastair M Kilpatrick, Hannah Esser, Kayleigh Thirlwell, Mark T Macmillan, Daniel Rodrigo-Torres, Benjamin J Dwyer, Victoria L Gadd, Candice Ashmore-Harris, Wei-Yu Lu, John P Thomson, Maurits A Jansen, Eoghan O'Duibhir, Philip J Starkey Lewis, L

Abstract

Biliary diseases can cause inflammation, fibrosis, bile duct destruction, and eventually liver failure. There are no curative treatments for biliary disease except for liver transplantation. New therapies are urgently required. We have therefore purified human biliary epithelial cells (hBECs) from human livers that were not used for liver transplantation. hBECs were tested as a cell therapy in a mouse model of biliary disease in which the conditional deletion of Mdm2 in cholangiocytes causes senescence, biliary strictures, and fibrosis. hBECs are expandable and phenotypically stable and help restore biliary structure and function, highlighting their regenerative capacity and a potential alternative to liver transplantation for biliary disease.

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