Lung models

Preclinical CRO Services

for Inflammatory Lung Diseases

 

Acute and chronic inflammatory lung diseases are among the most common medical conditions in the world. Rodent models of lung inflammation are helpful to decipher the mechanisms underlying the triggering and/or sustaining of the disease observed in patients.

Oncodesign Services offers several preclinical models available as CRO services, addressing a variety of lung diseases, and provides CRO support for the de novo development of new lung inflammation models recently described in literature.

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Typical readouts for lung inflammation

  • Body weight
  • Lung weight
  • Lung weight-to-body weight ratio
  • Clinical scoring
  • Edema
  • Fibrosis score
  • Mucus production
  • Viral load
  • Ex vivo lung function, including compliance and elasticity (FlexiVent, SCIREQ)
  • Broncho-alveolar fluid (BALF) cell count and cytokine secretion
  • CT scan
  • Gene expression in lungs, by qPCR/dPCR
  • Biomarker / drug monitoring

 

Common drug administration routes (PO, IV, IP) and also non-typical drug administration routes used for lung therapies:

  • Intra-tracheal
  • Intra-nasal
  • Osmotic mini-pumps

 

Discover Oncodesign Services offers for lung inflammation diseases

  • In Vitro capabilities
    • Cells:
      • HPASMC (Human Pulmonary Arterial Smooth Muscle Cells)
      • HPAEC (Human Pulmonary Arterial Endothelial Cells)
    • Assays:
      • Collagen formation (scar-in-a-jar assay)
      • Impedance (signaling) assay
      • Epithelial–mesenchymal Transition assay
      • Surrogate of pulmonary arterial hypertension (PAH)
  • In Vivo Models

    Oncodesign Services has developed robust models to provide CRO services that deliver high quality data.

    • Bronchiolitis model in mice, induced by Human Respiratory Syncytial Virus (RSV)
    • Allergic asthma model in mice, induced by House Dust Mice (HDM)
    • Corticoid-resistant asthma in mice, induced by Ovalbumin (OVA) + Influenzae
    • Asthma exacerbation model in mice, induced by RSV + HDM combination
    • Lung fibrosis model in mice, induced by Bleomycin delivered IT or by osmotic pumps

    If you cannot find the model you desire in this list, please get in touch.

Case studies for lung inflammation

  • #1 House dust-mite (HDM)-induced allergic asthma model

    HDM is one of the most important sources of indoor allergens and a significant factor underlying allergic rhinitis and allergic asthma.  HDM intranasal challenge can be used in BALB/c mice to reproduce many key features of clinical asthma:

    • HDM challenge (IN) administered 5 days per week during 3 weeks
    • Elevated levels of IgE
    • Airway inflammation
    • Goblet cell hyperplasia with mucus overproduction
    • Release of inflammatory mediators and cytokines primarily associated with Th2-type inflammation
    • Responsive to fluticasone (inhaled corticoid)

    Results show allergic signature in bronchoalveolar lavage fluid (BALF) and in plasma with BALF cell content & cytokine secretion, and with plasma IgE levels.

    Allergic signature inbronchoalveolar lavage (BAL) and in plasma :

    • BAL cell content & cytokine secretion
    • Plasma IgE levels
  • #2 Bronchiolitis model – Respiratory syncytial virus (RSV) infection in BALB/c mice

    Respiratory syncytial virus (RSV) is a virus responsible for severe respiratory symptoms including rhinitis, bronchiolitis and pneumonia.  About 65% of children are infected with RSV within the first year of life.

    The disease is modeled by delivering a high dose of RSV by intranasal instillation to BALB/c mice, which allows viral infection and bronchiolitis symptoms.  Excessive production of airway mucus is a feature of such inflammatory lung disease and is a key histology readout.  Ribavirin is typically used as a reference compound.

  • #3 Bleomycin-induced lung fibrosis model using intra-tracheal instillation

    To date, the mouse bleomycin-induced lung injury model remains the most frequently used animal model to investigate pulmonary fibrosis resulting from inflammation.

    Similar to the human disease, bleomycin exposure in mice is is associated to epithelial damage, inflammatory cell infiltration, and proliferation of fibroblasts and myofibroblasts, as well as extra-cellular matrix excessive deposition.

    Model setup: intra-tracheal (IT) administration of bleomycin on Day 0 in C57BL/6 male mice (n=8 animals/group as a minimum after randomization).

    CRO study design to obtain robust data

    • D0: single IT administration of bleomycin or saline under ketamine/xylazine anesthesia
    • D7: selection of good responders to bleomycin (based on % body weight loss)
    • Selection rate of ±65% – around 12 animals per group to get 8 selected animals per group
    • D7 to D21: treatment
    • Around D21: termination of animals

     

    Lung histology at D21 for anti-fibrotic drug evaluation

    • ALK5 (TGFb receptor I) inhibitor [SB-525334]: effective at 30 or 60mg/kg/day (with Cmax-driven dose-effect)
    • Nintedanib (Tyr kinase inhibitor): no effect at 60 or 100mg/kg/day
    • Pirfenidone (molecular target unknown): no effect at 300 or 500mg/kg/day