Human liver cells show potential to treat biliary disease

CRM and Scottish National Blood Transfusion Service (SNBTS) scientists have found that human liver cells- termed biliary cells- show potential to repair biliary injury and disease.

Biliary cells make up less than 5% of the liver but are vital to drain toxins from the liver. When these cells are damaged the whole liver can fail.

Current therapies are often poorly effective and at best slow the disease progression. Eventually, if the liver is severely damaged, liver transplantation is the only option for patients; however, given the shortage of organs, this is not always a possibility.

In this manuscript, researchers led by Professor Stuart Forbes, Sofia Ferreira-Gonzalez, John Hallett and the Scottish National Blood and Transplant Service (SNBTS) isolated and expanded human Biliary Epithelial Cells (hBEC) from human livers that can’t be transplanted. 

5% of all retrieved donor livers in UK have issues that make them unsuitable for transplantation. The team rescued these otherwise unusable human livers and used them to explore the regenerative properties of different cell types. In their study, the research team show that one of these cell types, the hBEC, can engraft in mouse liver and repair the damage when the regenerative capacities of the organ are profoundly impaired. These cells can be isolated in Good Manufacturing Process (GMP) compliant conditions and expanded to generate a library of cells.

To test the potential of the human biliary cells as a therapy for biliary disease, the cells needed to be transplanted into a new mouse model that reproduces the clinical scenario of biliary disease as closely as possible. 

When the mice displayed signs of biliary disease, human biliary cells were transplanted and the team monitored their engraftment, function and regenerative properties. The transplanted cells restored biliary structures and reduced scarring in the diseased mouse livers, while the mice had better liver function and were more likely to survive. 

This study demonstrates the regenerative potential of human Biliary Epithelial Cells to mediate repair and restore biliary function, offering a potential therapy to alleviate the burden of biliary disease.

If we can find ways of helping the liver to regenerate that would really alleviate the problem of large numbers of people with server liver damage.

Professor Stuart Forbes

This work was supported by the UK Medical Research Council, the Edinburgh Clinical Academic Track Cancer Research UK PhD fellowship, and Edinburgh and Lothians Health Foundation Liver Transplant Fund.

Hallet, Ferreira-Gonzalez et al (2022). Cell Stem Cell 29(3), 355-371 DOI: 10.1016/j.stem.2022.02.006 

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