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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 nodule formation, 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.
Many customers including global pharmaceuticals companies are using our CRO service.
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 nodule
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>

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 nodule/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

Examples of pharmacological studies using our NASH model
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
SGLT2 inhibitor
Drug efficacy
DPP-Ⅳinhibitor
Drug efficacy
Tyrosine kinase inhibitor
Drug efficacy
ACE inhibitor
Drug efficacy
Anti-inflammatory agents
Drug efficacy
FXR agonist
Drug efficacy
PXR antagonist
Drug efficacy
Hypolipidemic agents
Drug efficacy
RS kinase inhibitor
Drug efficacy
IFN-like agents
Drug efficacy
Chemokine antibodies
Drug efficacy
ECM-related enzyme
Drug efficacy
Opioid receptor antagonist
Drug efficacy
Anti-oxidant
Drug efficacy
Serotonin receptor antagonist
Drug efficacy
siRNA to fibrosis-related gene
Drug efficacy, Pharmacokinetics
ASOs
Basic research, Target discovery
Growth factor gene transfer
Therapeutic efficacy
Cancer
Gene expression profiling
EMT
Basic research, Target discovery
ECM: extracellular matrix, EMT: epithelial-mesenchymal transition, ASOs: Antisense oligonucleotides, RS: Ribosomal S6
For more information about the NASH model and our contract research services, contact us by e-mail: info@stelic.co.jp