Fibrosis models for pulmonary, skin, liver, renal, and genitourinary diseases
Fibrosis arises through complex interactions between multiple cell types, molecular mediators, and signaling pathways. Preclinical models play a critical role in understanding disease biology and supporting the development of new therapies for fibrotic disorders. At Oncodesign Services, we offer and develop various models of fibrotic diseases including skin fibrosis, lung fibrosis, liver fibrosis, NASH, kidney fibrosis, and fibrotic endometriosis for pharmacology studies.
Fibrosis: a disease with high unmet medical needs
Fibrosis is characterized by excessive formation and deposition of fibrous connective tissue (scarring) resulting in progressive architectural remodeling in tissues and organs. Fibrotic disorders, such as NASH, liver fibrosis, pulmonary fibrosis, skin fibrosis, scleroderma, renal interstitial fibrosis,and fibrotic endometriosis, result in loss of function of affected organs. There are no currently approved treatments for fibrosis.
The fibrosis cascade is typically initiated by inflammatory insults, resulting in upregulation of TGF-beta, which recruits macrophages that secrete metalloproteases (MMPs) that degrade the extracellular matrix (ECM) to remodel the tissue. This triggers differentiation and activation of myofibroblasts that deposit collagen fibers to cause scarring and organ stiffness.
Fibrosis models by disease indication
Fibrosis models constitute an essential tool for preclinical research, allowing you to study the development of fibrosis, replicate the fibrosis-related diseases observed in human patients, and develop new therapies.
Oncodesign Services offers validated models supported by high-quality readouts (including clinical, biomarker and functional and a range of preclinical and pharmacology services. We are also able to customize and develop de novo models as required. Examples of popular fibrosis models include:
- Respiratory fibrosis: bleomycin-induced lung fibrosis (intratracheal and minipump delivery)
- Skin fibrosis: bleomycin-induced scleroderma
- Liver fibrosis: CCl4-induced fibrosis, Non-Alcoholic Steatohepatitis (NASH)
- Kidney fibrosis: Unilateral ureteral obstruction (UUO)-induced renal fibrosis
- Endometriosis: syngeneic and xenogenic models
To supplement clinical readouts (body weight and clinical scoring) a number of biomarker readouts can be obtained by histology, IHC, ELISA, MSD, Bio-Plex, RT-qPCR/dPCR, and flow cytometry.
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Lung fibrosis models
Lung fibrosis can lead to chronic respiratory insufficiency, with limited treatment options available for patients.
At Oncodesign Services, we have extensive experience with administration formats for bleomycin-induced lung fibrosis models, i.e. by intratracheal and by subcutaneous osmotic mini-pumps. These administration routes result in different patterns of lesions, time-courses of disease induction, and different cohort selection methods.
Typical readouts include clinical scoring, lung imaging (CT-scan), histology, lung function assessment, and gene expression. Combining a variety of readouts allows us to provide robust preclinical models of lung fibrosis. Oncodesign Services has implemented and validated the flexiVent® system (Scireq™), which provides clinically relevant readouts of lung function. This approach allows us to evaluate the efficacy of candidate drugs along all relevant dimensions of the disease.
Bleomycin-induced lung fibrosis in mice: lung histology at day 21.
FlexiVent analysis of lung mechanics in bleomycin-induced lung fibrosis model in C57BL/6 mice: Static compliance degradation by Bleomycin administration and compliance improvement with SB-52334 (ALK5 inhibitor).
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Skin fibrosis (scleroderma) models
The bleomycin-induced scleroderma model is widely used in academia and industry. Mice are given daily subcutaneous injections of bleomycin for 6 weeks. The main readouts include clinical follow-up of body weight loss and signs of skin inflammation followed by hardening, histological quantifications of collagen deposition in the skin and the lungs, and skin thickening. Additionally, skin gene expression (qRT-PCR) can be performed to follow the kinetics of cytokine induction.
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Liver fibrosis models
The CCl4 model of liver fibrosis is a classical model widely used in preclinical drug testing. Mice are given repeated doses of CCl4 and liver fibrosis then typically appears after 6 weeks. This model is useful for testing therapies aimed at modulating collagen deposition and inflammatory pathways. ALK5 (TGFb receptor I) inhibitors, exploiting a well-known anti-fibrotic mechanism, decrease collagen production and are used as a reference therapy.
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NASH models
NASH, for Non-Alcoholic SteatoHepatitis, is a chronic liver disease that can lead to fibrosis and Hepato-Cellular Carcinoma (HCC). It is a major cause of liver disease in developed countries (around 20 million in US suffer from NASH and advanced fibrosis), with estimated prevalence of 24% of general population, with an increase of HCC incidence by 3% annually in the past 10 years.
Example of NASH components:
- Presence of steatosis (abnormal intracellular retention of lipids) and inflammation
- Inflammatory infiltrates
- Hepatocyte injury (hepatocyte ballooning and cell death)
- Progressive fibrosis (collagen fiber deposition)
In preclinical research, NASH models allow testing of new potential treatments before clinical trials.
Oncodesign Services provides a large portfolio of in vitro and in vivo models for inflammatory diseases, including chronic liver injury models such as the carbon tetrachloride and high fat diet-induced NASH model:
- STZ+HFD NASH (long term model leading to HCC)
- CCl4+HFD NASH
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Kidney fibrosis models
Oncodesign Services offers Kidney fibrosis model in rats, induced by Unilateral Ureteral Obstruction (UUO).
Pictured: Histology images showing kidney fibrosis induced by Unilateral Ureteral Obstruction (UUO).
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Endometriosis models
Endometriosis is a chronic inflammatory disease characterized by the growth of endometrial-like tissue outside the uterus. Progressive fibrosis contributes to lesion burden and is associated with chronic pain, digestive impairment, and infertility. The complex interplay between inflammation, angiogenesis, and tissue remodeling makes endometriosis a challenging disease to model and treat.
The endometriosis models offered by Oncodesign Services enable the evaluation of candidate therapies in clinically relevant settings. Typical readouts include lesion burden and volume, histopathology, collagen deposition, inflammatory biomarkers, and molecular analyses. These approaches provide valuable insights into disease progression and therapeutic response.
Discuss your fibrosis research with our scientific team
Selecting the right model and endpoints is critical to generating meaningful preclinical data. With experience across multiple organ systems and fibrosis-related diseases, our teams support the design and implementation of studies tailored to the scientific questions underpinning your program.
Get in touch to discuss your fibrosis research and explore the most appropriate models and translational readouts for your objectives.
Frequently asked questions about our fibrosis models
Which fibrotic diseases can be modeled?
Fibrosis models can be developed for multiple organ systems, including:
- Pulmonary fibrosis
- Liver fibrosis
- Kidney fibrosis
- Skin fibrosis
- Systemic sclerosis–related fibrosis
- Endometriosis-related fibrosis
Customized models may also be designed based on specific therapeutic targets or disease pathways.
What endpoints are commonly assessed in fibrosis studies?
Typical endpoints include:
- Histopathology and fibrosis scoring
- Collagen deposition analysis
- Cytokine and growth factor profiling
- Gene and protein expression
- Fibroblast activation markers
- Tissue remodeling assessment
- Imaging and morphometric analysis
- For lung fibrosis models: lung function (elastance, compliance)
What species are commonly used in fibrosis research?
Mouse and rat models are frequently used for fibrosis studies due to their well-characterized disease responses and availability of validated protocols. Additional species may be available depending on study goals.
