A5031401964- Liver physiology and pathology
- Liver Disease Diagnosis and Treatment
- Tissue Engineering and Regenerative Medicine
- Liver Disease and Transplantation
- Cancer, Hypoxia, and Metabolism
- Endoplasmic Reticulum Stress and Disease
- Liver Diseases and Immunity
- Neuroendocrine Tumor Research Advances
- Diet, Metabolism, and Disease
- 3D Printing in Biomedical Research
- Pancreatic function and diabetes
- Phagocytosis and Immune Regulation
- DNA Repair Mechanisms
- Cholangiocarcinoma and Gallbladder Cancer Studies
- RNA modifications and cancer
- Diet and metabolism studies
- Metabolism and Genetic Disorders
- Mitochondrial Function and Pathology
- Electrospun Nanofibers in Biomedical Applications
- Chemokine receptors and signaling
- Macrophage Migration Inhibitory Factor
- Peroxisome Proliferator-Activated Receptors
- Cancer Mechanisms and Therapy
- Organ Transplantation Techniques and Outcomes
- Wnt/β-catenin signaling in development and cancer
The Royal Free Hospital
2015-2024
University College London
2015-2024
Amsterdam University Medical Centers
2023
University of Florence
2004-2022
University of Milan
2022
Institute for Liver Health
2017
Roland Hill (United Kingdom)
2014-2015
Chiba University
2015
Ocera Therapeutics (United States)
2015
Grifols (United States)
2015
Abstract Liver synthetic and metabolic function can only be optimised by the growth of cells within a supportive liver matrix. This achieved utilisation decellularised human tissue. Here we demonstrate complete decellularization whole lobes to form an extracellular matrix scaffold with preserved architecture. Decellularized cubic scaffolds were repopulated for up 21 days using cell lines hepatic stellate (LX2), hepatocellular carcinoma (Sk-Hep-1) hepatoblastoma (HepG2), excellent viability,...
Leptin upregulates collagen expression in hepatic stellate cells (HSCs), but the possible modulation of other actions has not been elucidated. The aim this study was to investigate and function leptin receptors (ObR) human HSCs biological regulated by leptin. Exposure resulted upregulation monocyte chemoattractant protein 1 (MCP-1) expression. also increased gene proangiogenic cytokines vascular endothelial growth factor (VEGF) angiopoietin-1, VEGF upregulated at level. Activated express...
Autoimmune liver diseases (AILDs) are chronic pathologies characterized by fibrosis and cirrhosis due to immune-mediated damage. In this study, we addressed the question whether mucosal-associated invariant T (MAIT) cells, innate-like functionally altered in patients with AILD MAIT cells can promote through activation of hepatic stellate (HSCs). We analyzed phenotype function from healthy controls multicolor flow cytometry investigated interaction between human primary (hHSCs). show that...
Research Article25 May 2016Open Access Source DataTransparent process Endoplasmic reticulum stress enhances fibrosis through IRE1α-mediated degradation of miR-150 and XBP-1 splicing Femke Heindryckx Department Medical Cell Biology, Uppsala University, Uppsala, Sweden Search for more papers by this author François Binet Markella Ponticos Centre Rheumatology Connective Tissue Diseases, University College London, UK Krista Rombouts Institute Liver Digestive Health, Joey Lau Johan Kreuger...
Focal adhesion kinase (FAK) is a key molecule in focal adhesions and regulates fundamental processes cells such as growth, survival, migration. FAK one of the first molecules recruited to response external mechanical stimuli therefore pivotal mediator cell mechanosignaling, relays these other mechanotransducers within cytoplasm. Yes-associated protein (YAP) has been identified recently core mechanotransducers. YAP translocates nucleus following changes mechanics promote expression genes...
Abstract Liver fibrosis is characterised by a dense and highly cross-linked extracellular matrix (ECM) which promotes progression of diseases such as hepatocellular carcinoma. The fibrotic microenvironment an increased stiffness, with rigidity associated disease progression. External stiffness known to promote hepatic stellate cell (HSC) activation through mechanotransduction, leading secretion ECM components. HSCs are key effector cells maintain the composition in health disease, not only...
Abstract The development of human liver scaffolds retaining their 3-dimensional structure and extra-cellular matrix (ECM) composition is essential for the advancement tissue engineering. We report design validation a new methodology rapid accurate production acellular cubes (ALTCs) using normal unsuitable transplantation. application high shear stress key methodological determinant accelerating process decellularization while maintaining ECM protein composition, 3D-architecture...
Abstract Epigenetic modifications such as DNA and histone methylation functionally cooperate in fostering tumor growth, including that of hepatocellular carcinoma (HCC). Pharmacological targeting these mechanisms may open new therapeutic avenues. We aimed to determine the efficacy potential mechanism action our dual G9a histone‐methyltransferase DNA‐methyltransferase 1 (DNMT1) inhibitor human HCC cells their crosstalk with fibrogenic cells. The expression DNMT1 , along molecular adaptor...
In nonalcoholic fatty liver disease (NAFLD), fibrosis is the most important factor contributing to NAFLD-associated morbidity and mortality. Prevention of progression reduction in are main aims treatment. Even early stages NAFLD, hepatic systemic hyperammonemia evident. This due reduced urea synthesis; as ammonia known activate stellate cells, we hypothesized that may be involved NAFLD.In a high-fat, high-cholesterol diet-induced rodent model observed progressive stepwise expression activity...
Hepatic stellate cells (HSC) transdifferentiation into myofibroblasts is central to fibrogenesis. Epigenetic mechanisms, including histone and DNA methylation, play a key role in this process. Concerted action between DNA-mehyltransferases like G9a DNMT1 common theme gene expression regulation. We aimed study the efficacy of CM272, first-in-class dual reversible G9a/DNMT1 inhibitor, halting fibrogenesis.G9a were analysed cirrhotic human livers, mouse models liver fibrosis cultured HSC. was...
Background and aims The PNPLA3 rs738409 C>G (encoding for I148M) variant is a risk locus the fibrogenic progression of chronic liver diseases, process driven by hepatic stellate cells (HSCs). We investigated how I148M affects HSCs biology using transcriptomic data validated findings in 3D-culture models. Methods RNA sequencing was performed on 2D-cultured primary human biopsies obese individuals, genotyped variant. Data were wild type (WT) or carrying I148M-PNPLA3 cultured 3D extracellular...
Hepatic stellate cells are the major cellular sources of extracellular matrix in chronic liver diseases leading to fibrosis. We explored antifibrogenic effect two histone deacetylase inhibitors, sodium butyrate and trichostatin A (TSA), on this cell type vitro. Primary hepatic as well culture activated were exposed (0.01–1 mmol/L) or TSA (1–100 nmol7sol;L); their collagen types I III smooth muscle α–actin was examined by quantitative immunoprecipitation Northern analysis. Their...
Reactive oxygen species are implicated in the pathogenesis of several diseases, including Alzheimer's disease, multiple sclerosis, human immunodeficiency virus, and liver fibrosis. With respect to fibrosis, we have investigated differences antioxidant enzymes expression stellate cells (SCs) parenchymal from normal CCl<sub>4</sub>-treated rat livers. We observed an increase catalase activated SCs. Treatment with transforming growth factor-β (TGF-β) increased production...
Nonalcoholic steatohepatitis (NASH) is the most severe form of nonalcoholic fatty liver disease (NAFLD), which to date has no approved drug treatments. There an urgent need for better understanding genetic and molecular pathways that underlie NAFLD/NASH, currently available preclinical models, be they in vivo or vitro , do not fully represent key aspects human state. We have developed a co‐culture NASH model using primary hepatocytes, Kupffer cells hepatic stellate cells, are cultured...
Non-alcoholic fatty liver disease (NAFLD) is a very common indication for transplantation. How fat-rich diets promote progression from to more damaging inflammatory and fibrotic stages poorly understood. Here, we show that disrupting phosphorylation at Ser196 (S196A) in the X receptor alpha (LXRα, NR1H3) retards NAFLD mice on high-fat-high-cholesterol diet. Mechanistically, this explained by key histone acetylation (H3K27) transcriptional changes pro-fibrotic pro-inflammatory genes....
An altered liver microenvironment characterized by a dysregulated extracellular matrix (ECM) supports the development and progression of hepatocellular carcinoma (HCC). The experimental platforms able to reproduce these physio-pathological conditions is essential in order identify validate new therapeutic targets for HCC. aim this work was vitro model based on engineering three-dimensional (3D) healthy cirrhotic human scaffolds with HCC cells recreating micro-environmental features favoring...