Longitudinal monitoring of liver function in vivo is hindered by the lack of high-resolution non-invasive imaging techniques. Using the anterior chamber of the mouse eye as a transplantation site, we have established a platform for longitudinal in vivo imaging of liver spheroids at cellular resolution. Transplanted liver spheroids engraft on the iris, become vascularized and innervated, retain hepatocyte-specific and liver-like features and can be studied by in vivo confocal microscopy. Employing fluorescent probes administered intravenously or spheroids formed from reporter mice, we showcase the potential use of this platform for monitoring hepatocyte cell cycle activity, bile secretion and lipoprotein uptake. Moreover, we show that hepatic lipid accumulation during diet-induced hepatosteatosis is mirrored in intraocular in vivo grafts. Here, we show a new technology which provides a crucial and unique tool to study liver physiology and disease progression in pre-clinical and basic research.
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http://dx.doi.org/10.1038/s41467-024-45122-4 | DOI Listing |
Methods Mol Biol
January 2025
Faculty of Medicine, Department of Medical Biology, Izmir Tinaztepe University, Izmir, Turkey.
In this chapter, we present a detailed protocol for establishing a three-dimensional (3D) multicellular tumor spheroids (MCTSs) model to simulate the tumor microenvironment (ME) associated with metabolic dysfunction-associated steatotic liver disease (MASLD) for the study of hepatocellular carcinoma (HCC) and colorectal cancer (CRC) cell aggressiveness, growth, and metastasis potential. The MASLD microenvironment (MASLD-ME) is recreated by embedding hepatic stellate cells in a collagen I matrix within a Boyden chamber system. The metabolic medium mimics MASLD conditions, enriched with high glucose, fructose, insulin, and fatty acids, to simulate metabolic stresses associated with the disease.
View Article and Find Full Text PDFSci Rep
January 2025
PredictCan Biotechnologies SAS, Biopôle Euromédecine, Grabels, France.
Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death worldwide. Treating HCC is challenging because of the poor drug effectiveness and the lack of tools to predict patient responses. To resolve these issues, we established a patient-centric spheroid model using HepG2, TWNT-1, and THP-1 co-culture, that mimics HCC phenotype.
View Article and Find Full Text PDFJHEP Rep
January 2025
Vrije Universiteit Brussel, Liver Cell Biology research group, Laarbeeklaan 103, 1090 Brussel, Belgium.
Toxicol Mech Methods
January 2025
Department of Life Sciences, of the University of Coimbra, Coimbra, Portugal.
Mitochondria are affected by chemical substances and play a critical role in drug-induced liver injury (DILI). Chemical substances can have a significant impact on various cellular processes, such as the disruption of oxidative phosphorylation, oxidative stress, and alteration of glucose metabolism. Given the consequences of these effects, it is crucial to understand the molecular pathways of chemical substances in the context of hepatotoxicity to prevent and treat DILI.
View Article and Find Full Text PDFBME Front
December 2024
Department of Aerospace and Mechanical Engineering, University of Southern California, Los Angeles, CA 90089, USA.
Deep-tissue solid cancer treatment has a poor prognosis, resulting in a very low 5-year patient survival rate. The primary challenges facing solid tumor therapies are accessibility, incomplete surgical removal of tumor tissue, the resistance of the hypoxic and heterogeneous tumor microenvironment to chemotherapy and radiation, and suffering caused by off-target toxicities. Here, sonodynamic therapy (SDT) is an evolving therapeutic approach that uses low-intensity ultrasound to target deep-tissue solid tumors.
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