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Human biliary epithelial cells from discarded donor livers rescue bile duct structure and function in a mouse model of biliary disease
Cell Stem Cell ( IF 23.9 ) Pub Date : 2022-03-03 , DOI: 10.1016/j.stem.2022.02.006
John M Hallett 1 , Sofia Ferreira-Gonzalez 1 , Tak Yung Man 1 , Alastair M Kilpatrick 1 , Hannah Esser 1 , Kayleigh Thirlwell 2 , Mark T Macmillan 1 , Daniel Rodrigo-Torres 1 , Benjamin J Dwyer 3 , Victoria L Gadd 1 , Candice Ashmore-Harris 1 , Wei-Yu Lu 4 , John P Thomson 5 , Maurits A Jansen 6 , Eoghan O'Duibhir 1 , Philip J Starkey Lewis 1 , Lara Campana 1 , Rhona E Aird 1 , Thomas S R Bate 7 , Alasdair R Fraser 2 , John D M Campbell 2 , Gabriel C Oniscu 8 , David C Hay 1 , Anthony Callanan 7 , Stuart J Forbes 1
Affiliation  

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.



中文翻译:

来自废弃供体肝脏的人胆道上皮细胞可挽救胆道疾病小鼠模型中的胆管结构和功能

胆道疾病可引起炎症、纤维化、胆管破坏,并最终导致肝功能衰竭。除了肝移植外,没有其他治疗胆道疾病的方法。迫切需要新的疗法。因此,我们从未用于肝移植的人肝脏中纯化了人胆道上皮细胞 (hBEC)。hBEC 作为细胞疗法在胆道疾病小鼠模型中进行了测试,其中胆管细胞中Mdm2的条件性缺失导致衰老、胆道狭窄和纤维化。hBEC 可扩展且表型稳定,有助于恢复胆道结构和功能,突出了它们的再生能力,是胆道疾病肝移植的潜在替代方案。

更新日期:2022-03-03
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