Ace Therapeutics specializes in developing customized liver failure models. By mimicking the complex interplay of hepatocyte injury, metabolic dysregulation, inflammatory responses, and multi-organ crosstalk, these models can provide unparalleled insights into the mechanistic underpinnings of liver failure progression. In addition to comprehensive model characterization and validation, we offer a suite of services to support your needs, from detailed omics-based biomarker identification to drug discovery and efficacy evaluation.
Introduction to Liver Failure
Liver failure, a serious condition in which the liver loses its function, is classified into acute liver failure (ALF) and chronic liver failure. Causes include viral infections, alcohol abuse, drug toxicity, and metabolic disorders. Pathological characteristics involve extensive hepatocyte damage, inflammation, fibrosis, and impaired metabolic and synthetic functions, leading to jaundice, coagulopathy, encephalopathy, and multi-organ failure. Effective research models are crucial for understanding this complex disease.
Figure 1. Partial hepatectomy for establishing mouse models of liver failure (Hefler J., et al., 2021)
How We Customize Animal Modes of Acute Liver Failure (ALF)
| Animal Species |
Advantages |
Limitations |
| Mice and Rats |
- Cost-effective and easy to handle.
- Well-established methods for genetic modifications.
- Commonly used in laboratories with a wealth of existing data.
|
Inflammatory and metabolic responses may differ from humans. |
| Humanized Mice |
- Immunodeficient mice engrafted with human cells or tissues, such as human hepatocytes, mimic human liver function.
|
Humanized mice may have different responses compared to wildtype mice |
| Rabbits |
- Specialized for viral hepatitis studies due to the presence of rabbit-specific diseases.
|
Rabbit-specific |
| Pigs |
- Closely resembles human liver structure and function.
- More socially acceptable than using dogs or non-human primates.
- More accessible than primates for research.
|
- High cost
- Difficult to operate
|
We employ various modeling methods tailored to simulate acute liver failure.
|
Chemically Induced Models |
- Acetaminophen (APAP) Overdose: Mimics drug-induced liver injury, a common cause of ALF.
- Carbon Tetrachloride (CCl4): Induces hepatotoxicity, mimicking toxin-induced liver failure.
- D-Galactosamine (d-Gal): Interferes with RNA synthesis by consuming uridine, leading to diffuse necrosis.
- Lipopolysaccharides (LPS) & D-Gal: Causes bacterial infiltration into the liver.
|
| Surgical Animal Models |
- Partial Hepatectomy: Simulates massive liver resection, commonly leading to ALF.
- Hepatic Ischemia/Reperfusion: Recreates conditions of blood flow interruption and restoration.
|
| Immunologic Models |
Concanavalin A (ConA) Administration: Induces immune-mediated liver injury, representing autoimmune hepatitis. |
| Viral Induced Models |
Rabbit Hemorrhagic Disease Virus (RHDV): Affects wild and domestic European rabbits (Oryctolagus cuniculus), causing acute hepatic necrosis, disseminated intravascular coagulation, and rapid death. |
| Genetic Models |
Knockout/Transgenic Rodents: Used to study specific gene functions and their role in liver failure. |
Our R&D Services for Liver Failure
We offer deep investigation of disease mechanism. Key services include analysis of metabolic alterations, inflammatory responses, and cell behavior changes across simulated failure progression.
We support biomarker discovery and qualification research using multi-omics techniques. Our services range from single-cell and spatial profiling to biomarker validation.
By leveraging our optimized liver failure models, we can provide a rigorous assessment of candidate therapeutics. The analyses generated aid in evaluating effects on endpoints such as hepatic function, regeneration, and survival.
- Drug Hepatotoxicity Evaluation
Through the application of our customized modeling platforms, Ace Therapeutics provides preclinical assessment of drug-induced hepatotoxicity risk. By quantifying drug effects on liver injured tissues, cells and molecular pathways, we efficiently identify compounds with development potential.
To learn more about how our liver failure disease model services can enhance your research and drug development efforts, contact Ace Therapeutics today. Our team of experts is dedicated to providing professional solutions and support tailored to your specific needs.
Reference
- Hefler J., et al. Preclinical models of acute liver failure: a comprehensive review. PeerJ. 2021, 9:e12579.
Related Services
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