Non-alcoholic fatty liver disease (NAFLD) and its progressive form non-alcoholic steatohepatitis (NASH) have presented a major and common health concern worldwide due to their increasing prevalence and progressive development of severe pathological conditions such as cirrhosis and liver cancer. Although a large number of drug candidates for the treatment of NASH have entered clinical trial testing, all have not been released to market due to their limited efficacy, and there remains no approved treatment for NASH available to this day. Recently, organoid technology that produces 3D multicellular aggregates with a liver tissue-like cytoarchitecture and improved functionality has been suggested as a novel platform for modeling the human-specific complex pathophysiology of NAFLD and NASH. In this review, we describe the cellular crosstalk between each cellular compartment in the liver during the pathogenesis of NAFLD and NASH. We also summarize the current state of liver organoid technology, describing the cellular diversity that could be recapitulated in liver organoids and proposing a future direction for liver organoid technology as an platform for disease modeling and drug discovery for NAFLD and NASH.
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http://dx.doi.org/10.7150/ijbs.85145 | DOI Listing |
Pathogens
December 2024
Massachusetts General Brigham for Children, 175 Cambridge Street, Boston, MA 02114, USA.
Hepatitis C virus (HCV) infects both pediatric and adult populations and is an important cause of chronic liver disease worldwide. There are differences in the screening and management of HCV between pediatric and adult patients, which have been highlighted in this review. Direct-acting antiviral agents (DAA) have made the cure of HCV possible, and fortunately, these medications are approved down to three years of age.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
Organoid technology, as an innovative approach in biomedicine, exhibits promising prospects in disease modeling, pharmaceutical screening, regenerative medicine, and oncology research. However, the use of tumor-derived Matrigel as the primary method for culturing organoids has significantly impeded the clinical translation of organoid technology due to concerns about potential risks, batch-to-batch instability, and high costs. To address these challenges, this study innovatively introduced a photo-crosslinkable hydrogel made from a porcine small intestinal submucosa decellularized matrix (SIS), fish collagen (FC), and methacrylate gelatin (GelMA).
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Laboratory of Genome Editing, Research Centre for Medical Genetics, Moskvorechye, 1, 115522 Moscow, Russia.
Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the gene. Currently, CFTR modulators are the most effective treatment for CF; however, they may not be suitable for all patients. A representative and convenient model is needed to screen therapeutic agents under development.
View Article and Find Full Text PDFJ Transl Med
January 2025
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China.
Background: The high mortality rate of metastatic colorectal cancer (CRC) is primarily attributed to resistance to chemotherapy, where cancer stem cells (CSCs) play a crucial role. Deubiquitinating enzymes are essential regulators of CSC maintenance, making them potential targets for eliminating CSCs and overcoming chemotherapy resistance. This study aims to identify key deubiquitinating enzymes regulating CSCs and drug resistance of CRC.
View Article and Find Full Text PDFStem Cell Reports
January 2025
Department of Medicine, Division of Nephrology, Institute for Stem Cell & Regenerative Medicine, and Kidney Research Institute, University of Washington School of Medicine, Seattle, WA 98109, USA; Plurexa LLC, Seattle, WA 98109, USA. Electronic address:
The mammalian target of rapamycin (mTOR) pathway is a therapeutic target in polycystic kidney disease (PKD), but mTOR inhibitors such as everolimus have failed to show efficacy at tolerated doses in clinical trials. Here, we introduce AV457, a novel rapalog developed to reduce side effects, and assess its dose-dependent safety and efficacy versus everolimus in PKD1 and PKD2 human kidney organoids, which form cysts in a PKD-specific way. Both AV457 and everolimus reduce cyst growth over time.
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