The creation of human liver models has long been a critical objective in academic, clinical, and pharmaceutical research, particularly for drug development, where accurate evaluation of hepatic metabolic dynamics is crucial. We have developed a bioengineered, perfused, organ-level human liver model that accurately replicates key liver functions, including metabolic activities, and protein synthesis, thus addressing some of the limitations associated with traditional liver monolayers, organoids, and matrix-embedded liver cells. Our approach utilizes liver-specific biomatrix scaffolds, prepared using an innovative protocol and fortified with matrix components that facilitate cellular interactions. These scaffolds, when seeded with human fetal liver cells or co-seeded with liver parenchymal and endothelial cell lines, enable the formation of three-dimensional (3D) human livers with enhanced cellular organization. The "recellularized tissue-engineered livers" (RCLs) have undergone various analyses, demonstrating the capability for establishing liver microenvironments . Within 7-14 days, the RCLs exhibit evidence of liver differentiation and metabolic capabilities, underscoring the potential for use in drug metabolism and toxicity studies. Although our study represents a significant step forward, we acknowledge the need for direct comparisons with existing models and further research to fully elucidate the spectrum of regenerative responses. The high drug-metabolizing enzyme activity of RCLs, as demonstrated in our study, provides a promising avenue for investigating drug-induced liver injury mechanisms, contributing to a more detailed understanding of early drug discovery processes.
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http://dx.doi.org/10.1016/j.bioactmat.2024.09.029 | DOI Listing |
Metab Brain Dis
January 2025
Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus N, Denmark.
Background & Aims: Hepatic encephalopathy (HE), one of the most serious prognostic factors for mortality in alcohol-related cirrhosis (ALD cirrhosis), is not recorded in Danish healthcare registries. However, treatment of HE with lactulose, the universal first-line treatment, can be identified through data on filled prescriptions. This study aimed to investigate if lactulose can be used as a surrogate marker of HE.
View Article and Find Full Text PDFDiscov Oncol
January 2025
Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Introduction: Colorectal cancer (CRC) is the second most common cause of cancer-related deaths globally. The gut microbiota, along with adenomatous polyps (AP), has emerged as a plausible contributor to CRC progression. This study aimed to scrutinize the impact of the FadA antigen derived from Fusobacterium nucleatum on the expression levels of the ANXA2 ceRNA network and assess its relevance to CRC advancement.
View Article and Find Full Text PDFBiochem Genet
January 2025
Department of Gynecology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
This study aimed to identify shared gene expression related to circadian rhythm disruption in polycystic ovary syndrome (PCOS) and non-alcoholic fatty liver disease (NAFLD) to discover common diagnostic biomarkers. Visceral fat RNA samples were collected from 12 PCOS and 14 non-PCOS patients, a sample size representing the clinical situation and sufficient to capture PCOS gene expression profiles. Along with liver transcriptome profiles from NAFLD patients, these data were analyzed to identify crosstalk circadian rhythm-related genes (CRRGs) between the diseases.
View Article and Find Full Text PDFClin Exp Med
January 2025
Department of Thoracic Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.
Introduction Recently, immune cells within the tumor microenvironment (TME) have become crucial in regulating cancer progression and treatment responses. The dynamic interactions between tumors and immune cells are emerging as a promising strategy to activate the host's immune system against various cancers. The development and progression of hepatocellular carcinoma (HCC) involve complex biological processes, with the role of the TME and tumor phenotypes still not fully understood.
View Article and Find Full Text PDFCurr Cardiol Rep
January 2025
Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
Purpose Of Review: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease, characterized by hepatic steatosis with at least one cardiometabolic risk factor. Patients with MASLD are at increased risk for the occurrence of cardiovascular events. Within this review article, we aimed to provide an update on the pathophysiology of MASLD, its interplay with cardiovascular disease, and current treatment strategies.
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