Cellular Homeostasis and Repair in the Biliary Tree

Abstract

During biliary tree homeostasis, BECs are largely in a quiescent state and their turnover is slow for maintaining normal tissue homeostasis. BTSCs continually replenish new BECs in the luminal surface of EHBDs. In response to various types of biliary injuries, distinct cellular sources, including HPCs, BTSCs, hepatocytes, and BECs, repair or regenerate the injured bile duct. BEC, biliary epithelial cell; BTSC, biliary tree stem/progenitor cell; EHBD, extrahepatic bile ducts; HPC, hepatic progenitor cell.

The biliary tree comprises intrahepatic bile ducts and extrahepatic bile ducts lined with epithelial cells known as biliary epithelial cells (BECs). BECs are a common target of various cholangiopathies for which there is an unmet therapeutic need in clinical hepatology. The repair and regeneration of biliary tissue may potentially restore the normal architecture and function of the biliary tree. Hence, the repair and regeneration process in detail, including the replication of existing BECs, expansion and differentiation of the hepatic progenitor cells and biliary tree stem/progenitor cells, and transdifferentiation of the hepatocytes, should be understood. In this paper, we review biliary tree homeostasis, repair, and regeneration and discuss the feasibility of regenerative therapy strategies for cholangiopathy treatment.

Keywords

biliary epithelial cells - homeostasis - injury - biliary regeneration

Abbreviations

BECs, biliary epithelial cells; BTSCs, biliary tree stem/progenitor cells; CFTR, cystic fibrosis transmembrane conductance regulator; EHBDs, extrahepatic bile ducts; HPCs, hepatic progenitor cells; Ig, immunoglobulin; IHBDs, intrahepatic bile ducts; PBC, primary biliary cholangitis; PD-1, programmed death-1; PSC, primary sclerosing cholangitis; scRNA-seq, single-cell RNA sequencing; TJs, tight junctions.

Publication History

Accepted Manuscript online:
07 June 2022

Article published online:
24 August 2022

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