ArticleCancers2021
Optimization and Validation of a Novel Three-Dimensional Co-Culture System in Decellularized Human Liver Scaffold for the Study of Liver Fibrosis and Cancer.
Article in Cancers, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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
18 citing papers in PubMed, 24 citations in OpenAlex.
- Hepatic stellate cells promote structural and functional remodeling of three-dimensional hepatocellular carcinoma coculture spheroids.Molecular biology reports · 2026Article
- Metabolic dysfunction-associated steatotic liver disease and steatohepatitis-associated hepatocarcinoma preclinical models.Nature reviews. Gastroenterology & hepatology · 2026Review
- Decellularized Liver Matrices for Expanding the Donor Pool-An Evaluation of Existing Protocols and Future Trends.Biomolecules · 2025Review
- Engineering liver disease models in vitro: emerging trends and innovations.eGastroenterology · 2025Review
- Challenges ofFrontiers in cell and developmental biology · 2025Review
- Decellularized extracellular matrix-based disease models for drug screening.Materials today. Bio · 2024Review
- Comparison of Engineered Liver 3D Models and the Role of Oxygenation for Patient-Derived Tumor Cells and Immortalized Cell Lines Cocultured with Tumor Stroma in the Detection of Hepatotoxins.Advanced biology · 2024Article
- Review
- Whole Liver Derived Acellular Extracellular Matrix for Bioengineering of Liver Constructs: An Updated Review.Bioengineering (Basel, Switzerland) · 2023Review
- Deciphering the underlying mechanism of liver diseases through utilization of multicellular hepatic spheroid models.BMB reports · 2023Review
- Three-Dimensional Cell Co-Culture Liver Models and Their Applications in Pharmaceutical Research.International journal of molecular sciences · 2023Review
- Review
- Influence of extracellular matrix composition on tumour cell behaviour in a biomimetic in vitro model for hepatocellular carcinoma.Scientific reports · 2023Article
- Decellularization of the Human Liver to Generate Native Extracellular Matrix for Use in Automated Functional Assays with Stellate Cells.Methods in molecular biology (Clifton, N.J.) · 2023Article
- High precision-cut liver slice model to study cell-autonomous antiviral defense of hepatocytes within their microenvironment.JHEP reports : innovation in hepatology · 2022Article
- Recent Advances in Liver Engineering With Decellularized Scaffold.Frontiers in bioengineering and biotechnology · 2022Review
- Inhibiting IRE1α-endonuclease activity decreases tumor burden in a mouse model for hepatocellular carcinoma.eLife · 2020Article
- Exploring the memory of the extracellular matrix using MASH-derived decellularized scaffolds.Journal of tissue engineeringArticle
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
The introduction of new preclinical models for in vitro drug discovery and testing based on 3D tissue-specific extracellular matrix (ECM) is very much awaited. This study was aimed at developing and validating a co-culture model using decellularized human liver 3D ECM scaffolds as a platform for anti-fibrotic and anti-cancer drug testing. Decellularized 3D scaffolds obtained from healthy and cirrhotic human livers were bioengineered with LX2 and HEPG2 as single and co-cultures for up to 13 days and validated as a new drug-testing platform. Pro-fibrogenic markers and cancer phenotypic gene/protein expression and secretion were differently affected when single and co-cultures were exposed to TGF-β1 with specific ECM-dependent effects. The anti-fibrotic efficacy of Sorafenib significantly reduced TGF-β1-induced pro-fibrogenic effects, which coincided with a downregulation of STAT3 phosphorylation. The anti-cancer efficacy of Regorafenib was significantly reduced in 3D bioengineered cells when compared to 2D cultures and dose-dependently associated with cell apoptosis by cleaved PARP-1 activation and P-STAT3 inhibition. Regorafenib reversed TGF-β1-induced P-STAT3 and SHP-1 through induction of epithelial mesenchymal marker E-cadherin and downregulation of vimentin protein expression in both co-cultures engrafting healthy and cirrhotic 3D scaffolds. In their complex, the results of the study suggest that this newly proposed 3D co-culture platform is able to reproduce the natural physio-pathological microenvironment and could be employed for anti-fibrotic and anti-HCC drug screening.
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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.