Innovative Fibrosis Medicine Discovery

fibrosis disease models for liver, renal, pulmonary disorders

Fibrosis, characterized by tissue scarring, is usually chronic and progressive as clinical symptom. It could be caused by diseases, iatrogenic injury or trauma. Those fibrosis-associated diseases include cirrhosis (LF), hepatitis, nonalcoholic steatohepatitis (NASH), chronic kidney disease (CKD), myocardial infarction, heart failure, diabetes, celiac disease, scleroderma, idiopathic pulmonary fibrosis (IPF), and more. The relevant abnormalities affect about one fourth of the world’s population but there have been no effective drugs available until recently. The establishment and application of animal models related to human diseases have attracted more and more of the industry’s attention and has become an indispensable part in pathogenesis research and therapeutic drug discovery.

Our fibrosis models cover liver fibrosis, lung fibrosis, kidney fibrosis, skin fibrosis, peritoneal fibrosis, ocular retinal fibrosis, etc… All pathology and biochemical endpoints are relevant to those that appeared as the clinical characteristics. With the advantage of assay technology, especially qPCR, ELISA, western blotting, flow cytometry, LC-MS/MS, etc., the mechanism of drug action and biomarkers can be evaluated at both protein and gene levels.

Liver Fibrosis

  • Chemical induction
  • Metabolic induction
  • Surgery

Mouse | Rat


Liver Fibrosis ModelCarbon tetrachloride (CCl4) induction
Liver Fibrosis ModelThioacetamide (TAA) induction
Liver Fibrosis ModelHigh-fat & cholesterol diet (HFCD) induction, with hyperlipidemia
Liver Fibrosis ModelDiet and CCl4-induced liver fibrosis
Liver Fibrosis ModelDiet and STZ-induced pulmonary fibrosis
Liver Fibrosis ModelN-nitrosodiethylamine (DEN)-induced liver fibrosis
Liver Cirrhosis ModelCarbon tetrachloride (CCl4) induction
Primary Biliary Cholangitis (PBC) Model Biliary duct ligation (BDL)
Primary Sclerosing Cholangitis (PSC) Model 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) induction

Case Studies

CCl4-induced liver fibrosis in mice

CCl4-induced liver fibrosis model in C57/BL6J mice is well-recognition and widely used. Based on the requirement from our clients, WuXi Biology has provided a variety of models with different single dose treatment cycle, from 4 weeks up to 20 weeks, with the different CCl4-induced dose ranges by co-induction with the specific diets. We have accumulated much practical experience for clients during compound efficacy evaluation for liver fibrosis.

quantitative morphormetry of sirius red, to assess liver fibrosis in mice via CCl4
Figure 1. OCA as a positive reference drug, significantly reduces hepatic fibrosis induced by CCl4 in C57/BL6J mice

Bile duct ligation (BDL)-induced liver fibrosis in rats

This BDL induced model in SD rats, has been widely used for severe liver fibrosis. Based on the requirements from clients, we refined the surgical steps of bile duct ligation (BDL) and reduced the mortality rate to 10%. This was superior to the mortality rate (50%), which was reported in the literature. The reference drug, Tropifexor, showed good efficacy.

bile duct ligation, BDL-induced liver fibrosis in rats, biochemical analysis
Figure 2a. Reference drug, Tropifexor, significantly improve liver function by measuring
bile duct ligation, BDL-induced liver fibrosis in rats, histopathology analysis
Figure 2b. Reference drug, Tropifecor, significantly reduced liver fibrosis

Pulmonary Fibrosis

  • Chemical induction

Mouse | Rat


Induced Pulmonary Fibrosis Models (IPFM)Bleomycin (BLM)-induced pulmonary fibrosis
Induced Pulmonary Fibrosis Models (IPFM)Silica-induced lung fibrosis

Bleomycin (BLM)-induced pulmonary fibrosis model in mice

BLM-induced fibrosis in C57/BL6J mice is widely used and very popular for the research in pulmonary fibrosis. After optimization, the mortality of the model was improved and reduced significantly to <10% compared to the literature which is 30-50%. The reference drug, Nintedanib, showed good efficacy.

Bleomycin (BLM)-induced pulmonary fibrosis model in mice, data using Nintedanib
Figure 3. Nintedanib 60mpk PO/QD significantly reduced lung fibrosis in BLM model.

Renal Fibrosis

  • Surgery
  • Chemical induction

Mouse | Rat


Induced Renal Fibrosis Models (IRFM)Unilateral ureteral obstruction (UUO)-induced renal fibrosis
Induced Renal Fibrosis Models (IRFM)5/6 nephrectomy-induced renal fibrosis
Induced Renal Fibrosis Models (IRFM)Purine-induced renal fibrosis

Others Fibrosis Models

  • Chemical induction

Mouse | Rat


Induced Skin Fibrosis Models (ISFM)Silica-induced skin fibrosis model 
Induced Peritonal Fibrosis Models (IPFM)Chlorhexidine gluconate-induced peritoneal fibrosis model
Induced Ocular Retinal Fibrosis Model (IORFM)Sodium iodate (NaIO3)-induced retinalfubrosis in mice

Peritoneal fibrosis model induced by chlorhexidine gluconate in mice

By using ICR mice, this model has been recognized and widely used for peritoneal fibrosis. Its stability and high reliability have been demonstrated through our work with clients. See below for typical data after the treatment with TGFβ inhibitors.

Peritoneal fibrosis model induced by chlorhexidine gluconate in mice
Figure 4. TGFβ inhibitors significantly reduced peritoneal fibrosis in a chlorhexidine gluconate-induced mouse model.

Test Parameters

Mouse | Rat

Animal characteristics
Body weight, tissue weight
Liver, lung, kidney, eye function and biomarker analysis
Determination of hydrooxyproline and/or collagen content
Gene expression (QT-PCR, Microarray, etc.)
Protein and metabolite profiling (WB, ELISA, mass spectrometry, etc.)
Pathological analysis
H&E staining/Analysis in tissues
Periodic Acid Schiff (PAS) staining for “Glomerulosclerosis Assessment”
Collagen deposition evaluation in tissues by “Picrosirius Red” staining and/or “Mason Trichrome” staining
Tissue a-SMAIHC staining and quantification
Other relavant IHC stains and makers for specific targets, i.e. collagen subtypes, macrophage intersital infiltrates and other downstream signaling biomakers

in vitro cell culture models

In addition to animal models, we have also established in vitro cell models by using human and rodent cells, either primary fibroblast cells or cell line. It becomes more feasible, cost effective, and allows for greater throughput using a in vitro platform for drug screening and evaluation.

In vitro cell culture fibrosis models, using TGF-beta induced LX-2 cells and MRC-5 cells, anti-fibrotic effects
Figure 5. Antifibrotic effects of compounds by measuring the changes in CTGF gene expression in human hepatic stellate cells (LX-2) and lung fibroblasts (MRC-5) (pre-stimulated with TGF-β1).

If you’re interested in the field of fibrotic disease models, please don’t hesitate to contact us and connect with our experts for further scientific discussions.