Hepatic progenitor cells, stem cells, and AFP expression in models of liver injury

Abstract Background Hepatic schistosomiasis, a chronic liver injury induced by long-term Schistosoma japonicum (S. japonicum) infection, is characterized by egg granulomas and fibrotic pathology. Hepatic progenitor cells (HPCs), which are nearly absent or quiescent in normal liver, play vital roles in chronic and severe liver injury. But their role in the progression of liver injury during infection remains unknown. Methods In this study, the hepatic egg granulomas, fibrosis and proliferation of HPCs were analyzed in the mice model of S. japonicum infection at different infectious stages. For validating the role of HPCs in hepatic injury, tumor necrosis factor-like-weak inducer of apoptosis (TWEAK) and TWEAK blocking antibody were used to manipulate the proliferation of HPCs in wild-type and IL-33−/− mice infected with S. japonicum. Results We found that the proliferation of HPCs was accompanied by inflammatory granulomas and fibrosis formation. HPCs expansion promoted liver regeneration and inhibited inflammatory egg granulomas, as well as the deposition of fibrotic collagen. Interestingly, the expression of IL-33 was negatively associated with HPCs’ expansion. There were no obvious differences of liver injury caused by infection between wild-type and IL-33−/− mice with HPCs’ expansion. However, liver injury was more attenuated in IL-33−/− mice than wild-type mice when the proliferation of HPCs was inhibited by anti-TWEAK. Conclusions Our data uncovered a protective role of HPCs in hepatic schistosomiasis in an IL-33-dependent manner, which might provide a promising progenitor cell therapy for hepatic schistosomiasis.

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Hepatic progenitor cells in human fetal liver express the oval cell marker Thy-1

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00465.2005 ◽

2006 ◽

Vol 291 (1) ◽

pp. G45-G54 ◽

Cited By ~ 73

Author(s):

Neil M. Masson ◽

Ian S. Currie ◽

John D. Terrace ◽

O. James Garden ◽

Rowan W. Parks ◽

...

Keyword(s):

Stem Cells ◽

Progenitor Cells ◽

Fetal Liver ◽

Stem Cell Marker ◽

Cytokeratin 19 ◽

Hepatic Progenitor Cells ◽

Cell Marker ◽

Human Fetal Liver ◽

Diseased Liver ◽

Hepatocyte Nuclear Factor 4Α

Hepatic progenitor cells play a major role in regenerating diseased liver. In rodents, progenitors forming hepatocytes or cholangiocytes are identified by the stem cell marker Thy-1. The aim of this study was to ascertain whether progenitor cells expressing Thy-1 could be identified in human fetal liver. Midtrimester human fetal liver was immunostained for Thy-1, cytokeratins 18 and 19, vimentin, CD34, CD45, and fibrinogen. Thy-1+ and Thy-1+CD34+ populations were purified using fluorescence-activated cell sorting (FACS). Immunofluorescence and mRNA expression were used to examine the bipotential nature of purified stem cells. We found that Thy-1+ cells were concentrated in portal tracts but were also scattered in parenchyma. In FACS-prepared cells, 0.18–3.08% (median 0.65%, n = 14) of cells were Thy-1+. Immunophenotyping revealed that some Thy-1+ cells coexpressed cytokeratins 18 and 19, others, fibrinogen and cytokeratin 19. RT-PCR demonstrated that Thy-1+ cells expressed mRNA for Thy-1, cytokeratin 18, and cytokeratin 19, and Thy-1+CD34+ cells expressed mRNA for α-fetoprotein, transferrin, and hepatocyte nuclear factor-4α. Thy-1+ cells were identified in fetal liver. These cells expressed several lineage markers, including coexpression of biliary and hepatocellular proteins and mRNA. These data suggest that Thy-1 is a marker of liver stem cells in human fetal liver.

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Hepatic Progenitor Cells Promote the Repair of Schistosomiasis Liver Injury Through Inhibiting IL-33 Secretion

10.21203/rs.3.rs-137173/v1 ◽

2021 ◽

Author(s):

Beibei Zhang ◽

Xiaoying Wu ◽

Jing Li ◽

An Ning ◽

Bo Zhang ◽

...

Keyword(s):

Liver Injury ◽

Progenitor Cells ◽

Progenitor Cell ◽

Normal Liver ◽

Protective Role ◽

Hepatic Progenitor Cells ◽

Mice Model ◽

Blocking Antibody

Abstract Background: Hepatic schistosomiasis, a chronic liver injury induced by long-term Schistosoma japonicum (S. japonicum) infection, is characterized by egg granulomas and fibrotic pathology. Hepatic progenitor cells (HPCs), which are nearly absent and quiescent in normal liver, play vital roles in chronic and severe liver injury. But their role in the progression of liver injury during infection remained unknown.Methods: In this study, the hepatic egg granulomas, fibrosis and proliferation of HPCs were analyzed in S. japonicum infection mice model at different infection stages. For validating the role of HPCs in hepatic injury, TNFrelated weak inducer of apoptosis (TWEAK) and TWEAK blocking antibody were used to manipulate the proliferation of HPCs. Histologic pathology and the expression of IL-33 were examined. Results: We found that the proliferation of HPCs paralleled with inflammatory granulomas and fibrosis formation. Promoting HPCs expansion promote the liver regeneration and inhibit the hepatocytes injury, the inflammatory eggs granulomas and the deposition of fibrotic collagen. Interestingly, the expression of IL-33 decreased when HPCs were manipulated to proliferate. Thus, IL-33 might be involved in the liver repair dominated by HPCs. Conclusions: Collectively, our data uncovered a protective role of HPCs in hepatic schistosomiasis in an IL-33 related manner, which might provide a promising progenitor cell therapy for hepatic schistosomiasis.

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