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Liver Diseases |
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Acute and chronic liver diseases are frequent and potentially life threatening for humans. The underlying etiologies are diverse, ranging from viral infections, autoimmune disorders, and intoxications to imbalanced diets and others. Therefore, animal liver disease models are in needs to mimic human liver diseases. HD Biosciences has established multiple animal liver disease models including acute liver injury; obesity related liver damage; nonalcoholic steatohepatitis (NASH); alcoholic steatohepatitis (ASH), liver fibrosis, liver cirrhosis and hepatocellular carcinoma (HCC). These models posse distinct features and etiology of human liver diseases to help evaluate the efficacy of lead compounds in relevant clinical liver diseases and are designed for better understanding of underlying. |
mechanisms for new drugs to be used in clinic |
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In vitro biochemistry, cell-based and functional assays |
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MOA and functional analysis including evaluation of cell proliferation, cell apoptosis and |
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specific fibrogenic pathways |
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Characterization of markers involving in liver injury, fibrogenesis or fibrolysis at gene and |
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protein levels with qPCR, ELISA, western blot, LC/MS/MS, etc. |
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Human HSC LX-2, rat HSC T6, primary rodent HSC and hepatocyte systems |
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In vivo animal models |
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Acute liver injury models |
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Alcohol induced acute liver injury in Kunming mouse & non human primate (NHP) |
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CCl4 induced acute liver injury in rodents & NHP |
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Chronic fatty liver models |
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Obesity in liver damage rodent models |
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HFD-induced fatty liver in mice and rats |
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ob/ob mice, db/db mice with fatty liver |
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Obesity and liver damage in NHP model |
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HFD-induced fatty liver in cynomolgus monkeys |
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Chronic liver injury models |
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Liver fibrosis/cirrhosis models |
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CCl4 induced liver fibrosis (mice, rats) |
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CCl4 induced liver cirrhosis (mice, rats) |
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Bile duct ligation (BDL) induced liver fibrosis (mice, rats) |
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Fatty liver + CCl4 induced liver fibrosis (mice, rats, NHP) |
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Fatty liver + CCl4 induced liver cirrhosis (mice, rats) |
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Alcohol induced chronic liver damage (NHP) |
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Non Alcoholic steatohepatitis (NASH) / HCC models |
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Fatty liver with NASH model |
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DIO + CCl4 induced NASH in mice |
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DIO + CCl4 induced NASH in NHP |
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STZ + HFD induced NASH, fibrosis, cirrhosis and HCC in mice |
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Complicated factor induced chronic liver injury model |
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High fat diet+alcohol+CCl4 induced liver fibrosis in monkey model |
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Endpoint Measurement |
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Clinical observation and physical examination |
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Body weight, behavior, food intake, water intake, defecation |
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Liver weight and spleen weight, ascite measurement, portal vein pressure |
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Biomarker analysis |
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Serum ALT / AST analysis |
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Gene expression and profiling (RT-PCR, microarray gene expression, miRNA) |
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Protein and metabolite profiling (WB, ELISA, mass spectrometry) |
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Hepatic hydroxyproline detection |
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Histology analysis |
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H&E staining in liver tissues |
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Sirius red staining and Masson Trchrome staining for collagen deposition and quantification in liver tissue |
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α-SMA IHC staining and quantification in liver tissues |
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Other related IHC staining for focused targets and markers |
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Representative Data |
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Liver damage in obese mouse models |
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Fatty liver in obese mice |
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Animal: C57BL/6J, male, 4-6 weeks of age; Diet: high fat diet (HFD, D12492, 60 kcal%, Research Diets, Inc) over 16 weeks. Body weight is about 40 gram. Severe fatty liver is observed. |
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Liver fibrosis in obese mice (NASH) |
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Animal: C57BL/6J, HFD 20 weeks, CCl4 for 4 weeks. H&E: Hepatocyte balloon degeneration with portal area inflammatory cell infiltration. Sirius Red: Collagen deposition in portal and intra lobular area. PAS: Glycogen deposit in hepatocytes. |
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CCl4 induced chronic liver damage in mouse and rat models |
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CCl4 induced liver fibrosis in mice |
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Balb/c mice, CCl4 0.5ul/g (1:5) i.p. twice a week for 8 weeks. Blood serum ALT and AST elevated significantly. Liver collagen deposition and myofibroblast proliferation have been detected. |
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CCl4 induced liver cirrhosis in rats |
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SD rats, CCl4 1.5ul/g (1:1) o.p. twice a week for 8 weeks. Histologically, inflammatory cell infiltration, hepatocyte degeneration, fibrosis and cirrhosis were observed. |
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The Latest Generation of Auto Patch Clamp Platform Launched at HDB  |
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WuXi Biology/HD Biosciences Presented at Webinar of "New Technologies for Target Discovery and Validation" |
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HD Biosciences Merges with WuXi AppTec |
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