ArticleProceedings of the National Academy of Sciences of the United States of America2013
Bone marrow injection stimulates hepatic ductular reactions in the absence of injury via macrophage-mediated TWEAK signaling.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
101 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pooled it
- Autologous macrophage therapy for liver cirrhosis: a phase 2 open-label randomized controlled trial.Nature medicine · 2025Trial
- Harnessing macrophage signaling pathways and scalable engineering for next-generation immunotherapies.Signal transduction and targeted therapy · 2026Review
- Unveiling a novel macrophage-driven mechanism for obeticholic acid-induced liver injury in cholestatic: targeting NLRP12Cell biology and toxicology · 2026Article
- Article
- Cell Therapy in Advanced Cirrhosis: From Preclinical Evidence to Clinical Application.Gastro hep advances · 2026Review
- Inflammation and immunity in liver homeostasis and disease: a nexus of hepatocytes, nonparenchymal cells and immune cells.Cellular & molecular immunology · 2025Review
- Dissecting the mechanisms of MASLD fibrosis in the era of single-cell and spatial omics.The Journal of clinical investigation · 2025Review
- Cell therapy for liver disorders: past, present and future.Nature reviews. Gastroenterology & hepatology · 2025Review
- Portal Fibrosis and the Ductular Reaction: Pathophysiological Role in the Progression of Liver Disease and Translational Opportunities.Gastroenterology · 2025Review
- Not the end of the road for macrophage therapy in liver cirrhosis.Nature medicine · 2025Article
- Molecular mechanisms in liver repair and regeneration: from physiology to therapeutics.Signal transduction and targeted therapy · 2025Review
- CD300EExperimental & molecular medicine · 2025Article
- Cellular Plasticity in Gut and Liver Regeneration.Gut and liver · 2024Review
- Wharton's Jelly mesenchymal stem cell-derived extracellular vesicles induce liver fibrosis-resolving phenotype in alternatively activated macrophages.Journal of cellular and molecular medicine · 2024Article
- Exploiting in silico modelling to enhance translation of liver cell therapies from bench to bedside.NPJ Regenerative medicine · 2024Review
- A spatiotemporal atlas of cholestatic injury and repair in mice.Nature genetics · 2024Article
- Protozoan-Derived Cytokine-Transgenic Macrophages Reverse Hepatic Fibrosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Review
- GITRL impairs hepatocyte repopulation by liver progenitor cells to aggravate inflammation and fibrosis by GITRCell death & disease · 2024Article
41 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors.
Funding
Abstract
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.