ArticleCells2019
Cirrhotic Human Liver Extracellular Matrix 3D Scaffolds Promote Smad-Dependent TGF-β1 Epithelial Mesenchymal Transition.
Article in Cells, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed.
- A NIR fluorotag reporter CETIF6a enables bright pan-tumor labeling and functional proteomic profiling.Nature communications · 2026Article
- Metabolic dysfunction-associated steatotic liver disease and steatohepatitis-associated hepatocarcinoma preclinical models.Nature reviews. Gastroenterology & hepatology · 2026Review
- A Radiopaque and Thermoresponsive Nanogel-Based Pickering Emulsion for Permanent Arterial Embolization.ACS omega · 2026Article
- Alternatives to animal models in gastroenterology and hepatology research.Frontiers in pharmacology · 2026Review
- Serum Proteomic Profile Based on the TGF-β Pathway Stratifies Risk of Hepatocellular Carcinoma.Liver international : official journal of the International Association for the Study of the Liver · 2025Article
- Exploring Cirrhosis: Insights into Advances in Therapeutic Strategies.International journal of molecular sciences · 2025Review
- Proteomic analysis of liver fibrosis reveals EFEMP1 as a new modulator of focal adhesion and migration of hepatic stellate cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Article
- Protective effects ofCytotechnology · 2025Article
- Review
- The Prospect of Hepatic Decellularized Extracellular Matrix as a Bioink for Liver 3D Bioprinting.Biomolecules · 2024Review
- Scaffold-based 3D cell culture models in cancer research.Journal of biomedical science · 2024Review
- Review
- Hepatic inflammatory responses in liver fibrosis.Nature reviews. Gastroenterology & hepatology · 2023Review
- A new prediction model of hepatocellular carcinoma based on N7-methylguanosine modification.BMC gastroenterology · 2023Article
- Functional biomaterials for biomimetic 3D in vitro tumor microenvironment modeling.In vitro models · 2023Review
- Article
- Collagen matrix scaffolds: Future perspectives for the management of chronic liver diseases.World journal of clinical cases · 2023Review
- Influence of extracellular matrix composition on tumour cell behaviour in a biomimetic in vitro model for hepatocellular carcinoma.Scientific reports · 2023Article
- Reconstruction of the human nipple-areolar complex: a tissue engineering approach.Frontiers in bioengineering and biotechnology · 2023Article
Corrections and comments
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Authors and funding
27 authors.
Funding
Abstract
An altered liver microenvironment characterized by a dysregulated extracellular matrix (ECM) supports the development and progression of hepatocellular carcinoma (HCC). The development of experimental platforms able to reproduce these physio-pathological conditions is essential in order to identify and validate new therapeutic targets for HCC. The aim of this work was to validate a new in vitro model based on engineering three-dimensional (3D) healthy and cirrhotic human liver scaffolds with HCC cells recreating the micro-environmental features favoring HCC. Healthy and cirrhotic human livers ECM scaffolds were developed using a high shear stress oscillation-decellularization procedure. The scaffolds bio-physical/bio-chemical properties were analyzed by qualitative and quantitative approaches. Cirrhotic 3D scaffolds were characterized by biomechanical properties and microarchitecture typical of the native cirrhotic tissue. Proteomic analysis was employed on decellularized 3D scaffolds and showed specific enriched proteins in cirrhotic ECM in comparison to healthy ECM proteins. Cell repopulation of cirrhotic scaffolds highlighted a unique up-regulation in genes related to epithelial to mesenchymal transition (EMT) and TGFβ signaling. This was also supported by the presence and release of higher concentration of endogenous TGFβ1 in cirrhotic scaffolds in comparison to healthy scaffolds. Fibronectin secretion was significantly upregulated in cells grown in cirrhotic scaffolds in comparison to cells engrafted in healthy scaffolds. TGFβ1 induced the phosphorylation of canonical proteins Smad2/3, which was ECM scaffold-dependent. Important, TGFβ1-induced phosphorylation of Smad2/3 was significantly reduced and ECM scaffold-independent when pre/simultaneously treated with the TGFβ-R1 kinase inhibitor Galunisertib. In conclusion, the inherent features of cirrhotic human liver ECM micro-environment were dissected and characterized for the first time as key pro-carcinogenic components in HCC development.
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