Liver Progenitor Cells Yield Functional Hepatocytes in Response to Chronic Liver Injury in Mice

Español–Suñer, Regina; Carpentier, Rodolphe; Hul, Noémi Van; Legry, Vanessa; Achouri, Younès; Cordi, Sabine; Jacquemin, Patrick; Lemaigre, Frédéric P.; Leclercq, Isabelle

doi:10.1053/j.gastro.2012.08.024

Cited by 309 publications

(404 citation statements)

References 42 publications

Supporting

Mentioning

375

Contrasting

Unclassified

Order By: Relevance

“…The precise characterization of hepatic stem cells and HPCs remains contentious with numerous, often nonspecific markers used to identify this population, although the majority consensus is that HPCs exist within the biliary tree and DRs. Various cells of the DR have been demonstrated to be capable of hepatocellular regeneration (9,14,15,26). Following macrophage transfer we go on to show that accompanying the DR response identified histologically, there is an expansion of a defined Ter119 − /CD31 − /CD45 − /CD24 + /EpCAM + cell population in the healthy livers that contains HPCs.…”

Section: Discussionmentioning

confidence: 91%

“…Cytokeratins (CK) 7 and 19, EpCAM (Epithelial Cell Adhesion Molecule), Dlk1 (Delta Like Homolog), MIC1-1C3, and Sox9 [sex determining region Y (SRY) box] are all accepted, albeit unspecific, markers of DRs, and have been used to define essential mediators, including many cytokines, which control the DR response to experimental liver injury (5,(13)(14)(15). Among the most recently identified of these paracrine signals is TNF-like weak inducer of apoptosis (TWEAK), a cytokine of the TNF family, which directly stimulates proliferation of DRs in vivo and HPCs in vitro (16,17).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Bone marrow injection stimulates hepatic ductular reactions in the absence of injury via macrophage-mediated TWEAK signaling

Bird

Boulter

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

149

146

View full text Add to dashboard Cite

Tissue progenitor cells are an attractive target for regenerative therapy. In various organs, bone marrow cell (BMC) therapy has shown promising preliminary results, but to date no definite mechanism has been demonstrated to account for the observed benefit in organ regeneration. Tissue injury and regeneration is invariably accompanied by macrophage infiltration, but their influence upon the progenitor cells is incompletely understood, and direct signaling pathways may be obscured by the multiple roles of macrophages during organ injury. We therefore examined a model without injury; a single i.v. injection of unfractionated BMCs in healthy mice. This induced ductular reactions (DRs) in healthy mice. We demonstrate that macrophages within the unfractionated BMCs are responsible for the production of DRs, engrafting in the recipient liver and localizing to the DRs. Engrafted macrophages produce the cytokine TWEAK (TNF-like weak inducer of apoptosis) in situ. We go on to show that recombinant TWEAK activates DRs and that BMC mediated DRs are TWEAK dependent. DRs are accompanied by liver growth, occur in the absence of liver tissue injury and hepatic progenitor cells can be isolated from the livers of mice with DRs. Overall these results reveal a hitherto undescribed mechanism linking macrophage infiltration to DRs in the liver and highlight a rationale for macrophage derived cell therapy in regenerative medicine.liver regeneration | adult stem cell

show abstract

Section: Discussionmentioning

confidence: 91%

mentioning

confidence: 99%

Bone marrow injection stimulates hepatic ductular reactions in the absence of injury via macrophage-mediated TWEAK signaling

Bird

Boulter

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

149

146

View full text Add to dashboard Cite

show abstract

“…LPCs prospectively isolated from chronically injured rodent and human livers showed the ability of self-renewal and bidirectional differentiation in vitro and differentiate to mature hepatocytes (MHs) in vivo (4 -8) when they were transplanted into livers, where residential MHs proliferation was impaired. Recently, using a lineage tracing technique, it was demonstrated that LPCs supplied MHs in chronically injured livers of mice fed with choline-deficient ethionine-supplemented (CDE) diet (9). It is also demonstrated that in other rodent models of liver injuries induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-containing diet, bile duct ligation (BDL), and chronic injection of carbon tetrachloride, ductular reaction is prominently induced, which is often considered as a sign of activation of LPCs.…”

mentioning

confidence: 99%

Sry HMG Box Protein 9-positive (Sox9+) Epithelial Cell Adhesion Molecule-negative (EpCAM−) Biphenotypic Cells Derived from Hepatocytes Are Involved in Mouse Liver Regeneration

Tanimizu

Nishikawa

Ichinohe

et al. 2014

Journal of Biological Chemistry

View full text Add to dashboard Cite

“…Their origin and liver repopulation capacity have been controversially discussed (14). Studies using the choline-deficient, ethionine-supplemented model of chronic liver injury (15) reported that LPCs expressing osteopontin (16) or Foxl1 (17) contributed to hepatocellular regeneration. In addition, transplantation of clonogenic LPCs into hepatocyte-senescent murine livers, induced through deletion of the E3 ubiquitin ligase Mdm2, resulted in restoration of the hepatic parenchyma through generation of hepatocytic or biliary epithelia (18).…”

Section: Liver Progenitor Cells and Cancer Stem Cellsmentioning

confidence: 99%

Wnt/?-Catenin Signalling during Liver Metabolism, Chronic Liver Disease and Hepatocarcinogenesis

Shirolkar¹,

Pasic²,

Gogoi-Tiwari³

et al. 2018

jrenhep

View full text Add to dashboard Cite

Chronic liver diseases (CLDs) are increasing in prevalence and their end-stage complications, namely, cirrhosis, liver failure and hepatocellular carcinoma represent major global challenges. The most common initiators of progressive CLD are viral hepatitis and long-term alcohol abuse as well as steatosis and steatohepatitis. Irrespective of the underlying aetiology, a common feature of CLD is the formation of hepatic ductular reactions, involving the proliferation of liver progenitor cells (LPCs) and their signalling to fibrosis-driving hepatic stellate cells. The Wnt/β-catenin pathway has been found to regulate development, stemness and differentiation, and alterations in its activity have been associated with tumour development. Recent data highlight the role of Wnt/β-catenin signalling in hepatic metabolism, steatosis and cancer, and suggest targeting of this pathway as a promising molecular strategy to potentially inhibit CLD progression and hepatocarcinogenesis.

show abstract

Liver Progenitor Cells Yield Functional Hepatocytes in Response to Chronic Liver Injury in Mice

Cited by 309 publications

References 42 publications

Bone marrow injection stimulates hepatic ductular reactions in the absence of injury via macrophage-mediated TWEAK signaling

Bone marrow injection stimulates hepatic ductular reactions in the absence of injury via macrophage-mediated TWEAK signaling

Sry HMG Box Protein 9-positive (Sox9+) Epithelial Cell Adhesion Molecule-negative (EpCAM−) Biphenotypic Cells Derived from Hepatocytes Are Involved in Mouse Liver Regeneration

Wnt/?-Catenin Signalling during Liver Metabolism, Chronic Liver Disease and Hepatocarcinogenesis

Contact Info

Product

Resources

About