At Ace Therapeutics, we aim to advance research and drug development for cholangitis through the development of customized disease models. Our team of experts leverages a deep understanding of cholangitis pathogenesis to develop models that reflect the complex pathological changes seen in human patients. We offer a range of species, from rodents to large animals, allowing us to tailor our models to specific research needs, whether it is to investigate the intricate molecular mechanisms of the disease or to evaluate the efficacy of novel therapeutic candidates.
Introduction to Cholangitis
Cholangitis is an inflammation of the bile ducts that can result from various underlying causes. There are three main types of cholangitis:
- Acute cholangitis, often called ascending cholangitis, typically results from bacterial infection due to bile duct obstruction.
- Primary sclerosing cholangitis (PSC), is a chronic, progressive disease characterized by inflammation and fibrosis of the bile ducts, eventually leading to bile duct strictures and liver damage.
- Primary biliary cholangitis (PBC), formerly known as primary biliary cirrhosis, is an autoimmune disease marked by the gradual destruction of the small bile ducts within the liver, leading to cholestasis and potential cirrhosis.
Figure 1. Pathogenesis, mouse models, and treatment strategies for primary biliary cholangitis (PBC) (Li H., et al., 2021)
What We Can Do for Cholangitis Model Customization
We predominantly use rodents, such as mice and rats, for cholangitis modeling. These species are chosen due to their genetic similarity to humans, ease of genetic manipulation, and well-characterized immune systems, making them ideal for studying disease mechanisms and testing therapeutic interventions.
- Acute Cholangitis Model Customization
Ace Therapeutics offers extensive customization services for acute cholangitis models to meet the specific needs of our clients' research objectives. We induce cholangitis in animals using various methods, such as bile duct ligation or bacterial inoculation, to accurately mimic the pathophysiological conditions observed in human patients. We can adjust the severity and progression of the disease within the model, allowing for detailed studies of different disease stages.
- Primary Sclerosing Cholangitis (PSC) Model Customization
| Modeling Methods |
Service Details |
| Genetic Manipulation |
This involves introducing mutations into genes known to be associated with PSC. Techniques such as CRISPR-Cas9 are used to generate these genetic modifications, which result in a phenotype that closely resembles human PSC, including bile duct inflammation and fibrosis.
- MDR3 (ABCB4) gene-deficient mice
- GPBAR1(TGR5) gene-deficient mice
- Fucosyltransferase 2 gene-deficient mice
- Mucin 1 gene-deficient mice
- Gamma-Glutamyltransferase 1 gene-deficient mice
- Nucleotide-Binding Oligomerization Domain 2 (NOD2) gene-deficient mice
|
| Chemical Induction |
Agents such as thioacetamide (TAA) or bile duct ligation (BDL) are used to chemically induce PSC. TAA administration leads to chronic liver injury and fibrosis, while BDL causes obstruction of bile flow, mimicking the inflammatory and fibrotic processes seen in PSC. |
- Primary Biliary Cholangitis (PBC) Model Customization
| Medel Types |
Medel Details |
| Spontaneous Animal Models |
- NOD.Abd3 mice
- dnTGFβRII mice
- IL-2Rα-/- mice
- FoxP3-deficient mice
- AE2a, b-/- mice
- ARE-Del-/- mice
|
| Induced Animal Models |
- Chemical Induction: Administration of xenobiotics such as 2-octynoic acid conjugated to bovine serum albumin (BSA) can induce PBC-like disease in mice, triggering an immune response against bile duct cells.
- Autoantigen Administration: Immunization of mice with specific autoantigens, such as the E2 subunit of the pyruvate dehydrogenase complex (PDC-E2), can induce an autoimmune response mirroring the pathogenesis of PBC.
|
Model Validation & Pharmacodynamic Services
- Blood tests to measure liver function.
- Non-invasive imaging techniques such as ultrasound or MRI to track changes in liver morphology and bile duct structure.
- Histopathological analysis of liver tissues, including staining techniques to identify fibrosis, inflammation, and bile duct abnormalities.
- Molecular profiling to investigate changes in gene expression and protein levels in PSC and PBC.
By meticulously developing and validating cholangitis models, Ace Therapeutics provides researchers with powerful tools to explore the pathophysiology and evaluate potential therapeutic strategies. For more information or to discuss your specific research needs, please contact us today.
Reference
- Li H., et al. The pathogenesis, models and therapeutic advances of primary biliary cholangitis. Biomed Pharmacother. 2021, 140:111754.
Related Services
Our products and services are for research use only and can not be used for diagnostic or other purposes.
