Bleomycin-Induced model for Idiopathic Pulmonary Fibrosis (IPF)
What is bleomycin?
Bleomycin is a chemotherapeutic agent used to treat cancer, but one of it’s side effects is pulmonary toxicity. It’s currently thought that bleomycin damages the lung through oxidative stress, and the damage to the lung triggers an inflammatory and fibrotic response.
How our model works
Our model is induced with a single dose of bleomycin, administered intra-tracheally by microsprayer. The local administration of bleomycin causes direct damage to the alveolar epithelial cells, leading to the infiltration of inflammatory cells and the development of interstitial fibrosis.
The model offers two treatment regimens – preventative and therapeutic, with an established positive control for each.
Advantages of SMC’s platform
SMC ExpertiseYour study in safe hands
SMC has been conducting pharmacology studies for almost 15 years, and our IPF model has been used to evaluate over 90 substances of a variety of modalities. We draw on our broad experience to design and perform bespoke studies tailored to the needs of our clients and their compounds, and utilize our extensive background data set to effectively evaluate their effect.
Our expert technicians have years of experience inducing this model to create a robust and reproducible phenotype and our other area of expertise – histological analysis – is performed by our highly skilled histopathologist for a reliable evaluation of efficacy.
Uniform Disease InductionUtilizing the Microsprayer
Our bleomycin model is induced through intra-tracheal administration using a device called the microsprayer. The microsprayer allows quick, precise and air-free administration of aerosol bleomycin directly to the lungs, which produces a uniform and localized phenotype. This method is technically challenging, but our model is always created by the same highly-skilled technicians for reliable and well-distributed fibrosis.
Single-mouse SamplingPerform multiple analyses for each mouse
Our sampling technique for the IPF model allows us to perform a range of analysis items using the samples from a single mouse. By ligating the trachea, we instil fixative in only certain lobes of the lung. Using this method, we can perform histological, biochemical, gene expression, and BALF analysis all using a single mouse. Thanks to this technique, we can perform studies with as few as 12 mice per group.
MicroCTIn-life monitoring of fibrosis development
Many pre-clinical parameters for evaluating lung fibrosis are terminal, making it difficult to compare with a baseline and offer low clinical correlation. Our facility is equipped with a High Resolution Computer Tomography (HRCT) system, which we offer as a clinically relevant non-invasive endpoint for lung fibrosis studies. With CT, we can monitor the fibrosis in-life and evaluate the change in fibrosis severity, giving clients further insight into the effect of their drug candidates.
Established Positive ControlsFor reliable comparison of efficacy
We offer an established positive control for both dosing regimens in this model.
Preventative – Dexamethasone:
A corticosteroid used for it’s anti-inflammatory and immunosuppressant effects. Of those tested in our in-house investigations, Dexamethasone showed the best and most reproducible improvement in Ashcroft score.
Therapeutic – Nintedanib
A small molecule tyrosine-kinase inhibitor targeting VEGF, FGF and PDGF receptors. Nintedanib is a currently approved therapy for IPF, and shows reproducible improvement in the Ashcroft score.
Our standard study outline
We pride ourselves on our flexibility, and always work with our clients to design their ideal study. As such, our study’s are extremely customisable, but we often use our basic plan as a starting point for design discussions.
|Induction||BLM, i.t. via Microsprayer (Day 0)|
|Treatment||Day 0 – Day 21 (3 weeks, preventative)
Day 7 – Day 21 (2 weeks, therapeutic)
|Administration||oral, i.v., i.p., s.c., i.t.|
|Mice/group||N=12 (at induction)|
|Randomization||Body weight (day 0 or day 6)|
|Endpoints||Ashcroft score (Masson’s Trichrome stained lung)
Body weight changes
|Other analysis||BALF analysis (cell counts, ELISA)
Lung gene expression