Abstract
BackgroundExtensive bile duct proliferation is a key feature of the tissue reaction to clinical and experimental forms of liver injury. Experimental infection of mice by Schistosoma mansoni is a well-studied model of liver fibrosis with bile duct hyperplasia. However, the regulatory mechanisms of bile duct changes are not well understood. In this study we report the reproducible isolation of long-term cultures of cholangiocytes from mice livers with schistosomal fibrosis.MethodsWe have isolated a cholangiocyte cell line from Schistosoma-induced liver granulomas using a combination of methods including selective adhesion and isopyknic centrifugation in Percoll.ResultsThe cell line was characterized by morphological criteria in optical and transmission electron microscopy, ability to form well differentiated ductular structures in collagen gels and by a positive staining for cytokeratin 18 and cytokeratin 19. To our knowledge, this is the first murine cholangiocyte cell line isolated from schistosomal fibrosis reported in the literature.ConclusionAfter 9 months and 16 passages this diploid cell line maintained differentiated characteristics and a high proliferative capacity. We believe the method described here may be a valuable tool to study bile duct changes during hepatic injury.
Highlights
Extensive bile duct proliferation is a key feature of the tissue reaction to clinical and experimental forms of liver injury and in many cases, this proliferation may affect liver function [1,2]
Hyperplasia of oval cells has not been described in schistosomiasis, in accordance with absence of chronic parenchymal injury, and it is not probable that the described established cholangiocyte cell line derives from oval cells
We propose that cholangiocyte hyperplasia is maintained in schistosomal liver by activated connective tissue, generating a proliferative and fully differentiated cell population
Summary
Extensive bile duct proliferation is a key feature of the tissue reaction to clinical and experimental forms of liver injury. Experimental infection of mice by Schistosoma mansoni is a wellstudied model of liver fibrosis with bile duct hyperplasia. Extensive bile duct proliferation is a key feature of the tissue reaction to clinical and experimental forms of liver injury and in many cases, this proliferation may affect liver function [1,2]. Experimental infection of mice by Schistosoma mansoni is a well studied model of liver fibrosis with bile duct hyperplasia [13](Fig. 1A–F), cholangiocytes have not yet been isolated from schistosomal livers and characterized in vitro.
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