Metabolic dysfunction-associated fatty liver disease (MASLD) presents a growing global health challenge with limited therapeutic choices. This review delves into the array of ex vivo tools and models utilized in MASLD research, encompassing liver-on-a-chip (LoC) systems, organoid-derived tissue-like structures, and human precision-cut liver slice (PCLS) systems. Given the urgent need to comprehend MASLD pathophysiology and identify novel therapeutic targets, this paper aims to shed light on the pivotal role of advanced ex vivo models in enhancing disease understanding and facilitating the development of potential therapies.
View Article and Find Full Text PDFMetabolic dysfunction-associated steatohepatitis (MASH) is the progressed version of metabolic dysfunction-associated steatotic liver disease (MASLD) characterized by inflammation and fibrosis, but also a pathophysiological "hub" that favors the emergence of liver malignancies. Current research efforts aim to identify risk factors, discover disease biomarkers, and aid patient stratification in the context of MASH-induced hepatocellular carcinoma (HCC), the most prevalent cancer among MASLD patients. To investigate the tumorigenic transition in MASH-induced HCC, researchers predominantly exploit preclinical animal-based MASH models and studies based on archived human biopsies and clinical trials.
View Article and Find Full Text PDFNon-alcoholic fatty liver disease (NAFLD) is considered as the hepatic manifestation of metabolic syndrome, which is characterised by obesity, insulin resistance, hypercholesterolemia and hypertension. NAFLD is the most frequent liver disease worldwide and more than 10% of NAFLD patients progress to the inflammatory and fibrotic stage of non-alcoholic steatohepatitis (NASH), which can lead to end-stage liver disease including hepatocellular carcinoma (HCC), the most frequent primary malignant liver tumor. Liver sinusoidal endothelial cells (LSEC) are strategically positioned at the interface between blood and hepatic parenchyma.
View Article and Find Full Text PDFNon-alcoholic fatty liver disease (NAFLD) is a growing global health issue, and the impact of NAFLD is compounded by the current lack of effective treatments. Considerable limiting factors hindering the timely and accurate diagnosis (including grading) and monitoring of NAFLD, as well as the development of potential therapies, are the current inadequacies in the characterization of the hepatic microenvironment structure and the scoring of the disease stage in a spatiotemporal and non-invasive manner. Using a diet-induced NAFLD mouse model, we investigated the use of in vivo micro-computed tomography (CT) imaging techniques as a non-invasive method to assess the progression stages of NAFLD, focusing predominantly on the hepatic vascular network due to its significant involvement in NAFLD-related hepatic dysregulation.
View Article and Find Full Text PDFPurpose Of The Review: Mitochondrial dysfunction has long been proposed to play a crucial role in the pathogenesis of a considerable number of disorders, such as neurodegeneration, cancer, cardiovascular, and metabolic disorders, including obesity-related insulin resistance and non-alcoholic fatty liver disease (NAFLD). Mitochondria are highly dynamic organelles that undergo functional and structural adaptations to meet the metabolic requirements of the cell. Alterations in nutrient availability or cellular energy needs can modify their formation through biogenesis and the opposite processes of fission and fusion, the fragmentation, and connection of mitochondrial network areas respectively.
View Article and Find Full Text PDFExpectation on engineered tissue substitute continues to grow, and for an effective development of a functional tissue and to control its quality, cellular mechanoresponse plays a key role. Although the mechanoresponse - in terms of cell-tissue interaction across scales - has been understood better in recent years, there are still technical limitations to quantitatively monitor the processes involved in the development of both native and engineered tissues. Computational (in silico) studies have been utilised to complement the experimental limitations and successfully applied to the prediction of tissue growth.
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