Stelic Institute & Co..

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Stelic’s research team has established a novel animal model which shows similar histopathology to human non-alcoholic steatohepatitis (NASH). The model is non-genetic and develops NASH on a basis of insulin resistance, hyperglycemia and hyperlipidemia followed by severe liver fibrosis and cirrhosis, and finally hepatocellular carcinoma. Using this proprietary model mice, we can assist you with your preclinical pharmacological studies including protocol design, study conduct, data analyses and report generation.
This model is now commercially available only in Japan, that is provided by our partner, Charles River Laboratories.
So in US and EU, customers including global pharmaceuticals are using our CRO service about the model.


Features and advantages of Stelic’s NASH mouse are as follows
(also see diagram below)

 1. Histological phenotype similar to human NASH
 2. Clear disease onset with no exception
  <No need to monitor the onset of asymptomatic NASH>
 3. Sequential changes from steatosis to NASH/fibrosis and from NASH/fibrosis to cirrhosis
   occur within 2 weeks, respectively
  <Efficacy of drug candidates in the treatment can be evaluated in short term>
 4. NASH-derived liver tumor
  <A definitive endpoint of NASH therapy can be investigated>

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Stelic’s research team has:
・ SPF-grade mouse facility
・ A high degree of professionalism in therapeutic research of inflammation, fibrosis and
  cancer.
・ Technical proficiency of in vivo experiments
・ Expertise in histopathology with state-of-the-art technology for imaging analyses

Study design:
Stelic can assist you with protocol design to generate reliable results from each study. Common in vivo assays for the development of NASH (from steatosis to steatohepatitis/fibrosis) and the progression of NASH (from fibrosis to cirrhosis/HCC) include: histopathology, serum biochemistry, liver biochemistry, gene expression and additional parameters. All tests will be carried out at our own state-of-the-art facility located in Tokyo, Japan.

Assays and Endpoints
Histology
・ HE staining (NAFLD Activity Score)
・ Masson’s trichrome staining
・ Oil Red staining
・ Sirius Red staining
・ Immunostaining for inflammation, fibrosis and tumor markers

Serum biochemistory
・ Blood glucose
・ ALT
・ AST
・ Triglyceride
・ Insulin tolerance test

Liver biochemistry
・ Triglyceride
・ Collagen
・ Oxidative stress markers

Gene expression
・ Lipogenesis-related genes
・ Inflammation-related genes
・ Fibrosis-related genes

Additional parameters
・ Clinical observations
・ Body weight
・ Liver weight
・ Survival rate (for cancer research)

Collagen Content in the Liver Tissue
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Examples of pharmacological studies using our NASH model

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Target/Compounds Type of Investigation
ARB (Telmisartan) Drug efficacy, a recommended positive control
ARB (Candesartan) Drug efficacy
ARB (Valsartan) Drug efficacy
TZD (Pioglitazone) Drug efficacy
CB1 antagonist Drug efficacy
CB2 agonist Drug efficacy
Anti-oxidant Drug efficacy
Anti-inflammatory agents Drug efficacy
FXR agonist Drug efficacy
IFN-like agent Drug efficacy
Antibody to chemokine Drug efficacy
siRNA to fibrosis-related gene Drug efficacy, Pharmacokinetics
ECM-related enzyme Drug efficacy
Growth factor gene transfer Therapeutic efficacy
Cancer Gene expression profiling
EMT Basic research, Target discovery

ECM: extracellular matrix, EMT: epithelial-mesenchymal transition


For more information about the NASH model and our contract research services, contact us by e-mail: info@stelic.co.jp

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