Biliary epithelial cells (BECs) from human livers were able to restore biliary structure and function in a mouse model of biliary disease, as published in Cell Stem Cell.

“This demonstration of a human cell therapy leading to the rescue of animals from biliary disease offers future clinical therapeutic opportunities for the use of these cells as a regenerative therapy for biliary disease,” the authors said. This is the case with Alagille syndrome (ALGS).

The team of researchers from the UK purified BECs from human livers that were not used for liver transplantation. Although they could be isolated from all discarded livers, they seem to be particularly abundant in steatotic livers. They were found to be highly expandable and phenotypically stable using good manufacturing process (GMP)-compliant conditions.


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BECs from human livers were characterized by the expression of the epithelial cellular adhesion molecule (EpCAM) and the markers CD24 and CD133. The CD133+ population of human BECs showed greater regenerative potential than the CD133- population, which had lower colony-forming efficiency and lower survival capacity.

Transplantation of human BECs into an immunodeficient model of the biliary disease led to the resolution of biliary strictures, decreased hepatic fibrosis, improved biochemical liver function, and reduced overall mortality.

Human BECs could be isolated and expanded in GMP-compliant conditions from frozen liver sections and cryopreserved for later use: “These cryopreserved cells retain function after thawing, providing strong evidence that [human BECs] could be manufactured and supplied for therapeutic use in clinical trials for relevant conditions, and offers a previously unappreciated cellular therapeutic approach for treatment of liver disease,” the authors concluded.

Reference

Hallett JM, Ferreira-Gonzalez S, Man TY, et al. Human biliary epithelial cells from discarded donor livers rescue bile duct structure and function in a mouse model of biliary disease. Cell Stem Cell. 2022;29(3):355-371.e10. doi:10.1016/j.stem.2022.02.006