Fibrosis Models
Bleomycin-Induced Fibrosis (IPF)
Validated Model of Idiopathic Pulmonary Fibrosis/Lung Injury
Species Available: Mouse
Bleomycin is a chemotherapeutic agent used to treat cancers such as Hodgkins lymphoma. One of the side effects is pulmonary toxicity, which can be life threatening in approximately 10% of patients.
The mechanism of bleomycin-induced lung injury includes oxidative damage via oxidant-mediated DNA breaks, causing inflammatory reactions in the lungs.
Bleomycin has also been used to induce lung injury in rodents for basic research into pulmonary fibrosis for over a decade. At MLM Medical Labs, we have refined the oral aspiration administration to allow for more even distribution of disease throughout both right and left lungs, making bleomycin-induced injury in mice a reliable model for research. This is a great model for studying idiopathic pulmonary fibrosis (IPF).
Available Bleomycin Study Readouts
- Immunophenotyping of bronchoalveolar lavage fluid (BALF):
- Quantitation of T Cells, B Cells, Macrophage, Neutrophils, Eosinophils, Fibroblasts, etc
- Cytokine Expression Levels (ELISA/Multiplex) in:
- BALF
- Lung Tissue Homogenate
- Plasma/Serum
- Histology of lung:
- H&E for morphologic analysis, cellular infiltration, etc (Figure 1)
- Masson's Trichrome staining for collagen
- IHC for specific markers of interest such as CD3, CD11b, etc.
- Lung tissue biomarkers
- Blood biomarkers (protein or nucleic acid)
- Lung tissue cellularity
Systemic Sclerosis (SSc) In-Vivo Model
Mouse Model to explore pathogenic Mechanisms
Systemic Sclerosis (SSc) is an autoimmune disease characterized by vasculopathy, fibrosis of the skin and internal organs, inflammation and general immune system abnormalities. MLM Medical Labs uses the chemotherapeutic antibiotic bleomycin to induce SSc in CD-1 mice as a model to explore the pathogenic mechanisms involved in SSc. Implementing the use of osmotic mini-pumps containing bleomycin allows for a more stable and convenient SSc murine model that encompasses multiple features of human disease. This model may be used in therapeutic programs related to SSc, and more broadly, fibrotic diseases.
Model Validation Options:
- Multiplex cytokine profiling
- Histological analysis
- Additional fibrotic assessments
All of the below images are H&E samples taken from mice. They are representative of microscopic findings in the skin at day 10 in this model.
Figure 1. H-L: Bleomycin group
H. The boxed areas are shown as indicated.
I. Diffuse moderate edema in the deep dermis and in the subcutis and moderate multifocal inflammation.
J. High magnification of changes in the deep dermis.
NAFLD/NASH Models
Nutrient-deficient NASH Diets - NASH In-Vivo Model
Non-alcoholic fatty liver disease (NAFLD) is a chronic condition affecting more than 30% of adults in the Western world that is characterized by accumulation of excess fat in the liver (hepatic steatosis) of people who drink little to no alcohol. While typically not considered a serious condition, NAFLD can develop into non-alcoholic steatohepatitis (NASH), which is a fatty liver accompanied by inflammation and various degrees of fibrosis that may develop into cirrhosis or HCC. There are no current FDA approved treatments for NASH, making pre-clinical drug development a top priority in the field. NASH is modeled pre-clinically through diets, inflammatory results, use of transgenic mice or a combination thereof.
Available Nutrient-deficient NASH Diet Models
- Methionine and Choline Deficient Diet (MCD)
- Choline Deficient, High Fat Diet (CHDFD)
Available Redaout Options
- Body weight
- Liver enzyme assessment
- Liver histopathology
Below are histology images of livers from Normal Diet (A) and NASH Diet Animals (E) at 9 weeks in mice. Images are 20x high magnification.
Normal Diet Liver, 9 weeks
NASH Diet Liver, 9 weeks
Both models induce hepatic steatosis, liver damage and progressive fibrosis.
Contact us to learn more about study design and to discuss your research needs.