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Lung Toxicity

Assays

  • LDH release
  • ATP/MTT activity
  • TEER

Models

  • Small airway epithelial cells (Human) cultured on a ALI interface

Timeline

  • 2-4 months

Newcells has developed an air-liquid interface (ALI) culture as a valuable tool for modelling the small airways of the lung in vitro and evaluating the lung toxicity of potential drug candidates

Lung toxicity and lung fibrosis occur as a result of inhalation of particles, pathogens and therapeutics but also following repeated administration of systemic and oral drugs.

The first line of defence of the lung is provided by lung epithelial cells which line the airways. Any epithelial damage or loss of epithelial barrier integrity leads to an increased susceptibility to infection, an impairment of gas exchange and triggers an immune response leading to inflammation, tissue damage and possibly lung toxicity. A loss of epithelial barrier function and the initiation of inherent repair mechanisms are also contributing factors to lung fibrosis.

The high vascularisation of the lung increases it susceptibility to drug-induced lung toxicity, especially upon repeated administration. Therapeutic molecules can thus induce cytokine release,  initiate an immune response and even a breakdown of the epithelial barrier, similarly to inhaled particles and pathogens. It is therefore essential to develop advanced in vitro epithelial cell culture models such as our SAEC model to accelerate the development of safe drugs and to understand lung damage, repair and fibrosis.

Service outputs

  • LDH release assay
  • ATP activity quantification
  • MTT activity
  • TEER

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Small Airway Epithelial Cells immunostained to detect junctional protein ZO1, a marker for tight junctions

Multiple readouts

All major cell types

of the lung epithelia

24-well format

Air-liquid interface

Lung Toxicity Assay

Accelerate your lead compound selection by evaluating their safety and lung toxicity profile in a relevant model of the lung small airways

1.

Accurately investigate response to epithelial damage

2.

Easily evaluate lung safety/toxicity in vitro

3.

De-risk drug discovery

Service overview Close Open

Cultured on 3D permeable supports, our fully differentiated, polarised, human small airway epithelial cell (SAEC) model allows the addition of xenobiotics to either the apical or basolateral compartments to evaluate how they affect the epithelial barrier integrity  and if they trigger cytokine release in response to cell damage.

As a standard, we measure four readouts our assays to determine drug-induced lung toxicity. As an example, Puromycin, an antibiotic with known toxic side effects in the lung,  triggers  a dose dependent response as measured by TEER, LDH release and ATP/MTT activity.

 

Puromycin induces a dose-dependent response as measured by A) TEER, B) LDH release, C) cellular ATP activity and D) formazan formation. After stimulating Newcells’ SAEC-ALI model with specified concentrations of Puromycin for 72 hours, resultant cell and epithelium damage show a dose-dependent decrease in TEER, which is associated with an increase of LDH release. Data shows a dose-dependent reduction in ATP activity and cell viability.
Assay design
Models

Primary small airway epithelial cell model with an ALI (air liquid interface).

The model includes all major cell types of the lung epithelium:

  • Basal cells
  • Club cells
  • Goblet cells
  • Ciliated cells
Assay format

24-well

Species

Human

Assay readout
  • TEER
  • Cell viability (LDH, ATP, MTT, formazan)
  • Cytokine release
  • Gene expression
  • Immunocytochemistry
Biological variation

3 human healthy donors (recommended)

Technical replicates

3 technical replicates per condition (recommended)

Assay treatment window

72 hours

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