in vitro inhalation

In vitro Inhalation

The most common way the body is exposed either unintentionally or deliberately to airborne materials (e.g. airborne contaminants, diesel exhaust, inhaled therapeutics) is through inhalation.

Recent advances in human cell culture exposure and test systems have led to the development of new in vitro assay systems that are more predictive and appropriate for toxicity screening a wide variety of compounds (e.g. chemicals, nanomaterials, pharmaceuticals, feed additives and tobacco products). These new in vitro toxicology systems have been developed using animal- or human-based cellular systems in accordance with 21st century toxicology recommendations.

In vitro inhalation testing is the method of choice for toxicity screening inhaled materials as it provides numerous advantages over in vivo inhalation studies, primarily because the former is cost- and time-efficient and involves no ethical issues. In addition, these models offer great flexibility as they are available for different respiratory tract areas (i.e. nasal, tracheal, bronchial and pulmonary). Although in vitro lung models have limitations, namely that they do not fully reflect the complexity of the entire respiratory system, they do provide broad knowledge regarding inhalation toxicology, as they model the human respiratory system cellular structure and tissue architecture.

 

In vitro human inhalation model

Our inhalation toxicity team has extensive experience conducting in vivo toxicology inhalation studies using state-of-the-art technology (link web inhalation). Thus, we can transfer our expertise in generating a homogeneous, controlled and stable test atmosphere from in vivo to in vitro exposure systems.

Vivotecnia is developing in vitro inhalation toxicity services using lung cell lines and 3D-airway epithelium models:

  • Proximal lung tissue models: EpiAirwayTM (MatTek Corporation2); MucilAirTM (Epithelix3)
  • Distal lung tissue models: EpiAlveolarTM (MatTek Corporation2); SmallAirTM (Epithelix3)

These 3D airway epithelium models replicate the human tissue structure and cellular morphology. The air-liquid-interface (ALI) represents a more realistic exposure scenario for materials inhaled into the lung compared to submerged exposures.

Combining 3D airway epithelium models and ALI exposure offers new possibilities to test biological responses to inhaled materials under physiologically relevant conditions and, importantly, also provides an accurate assessment of acute respiratory toxicity and predicts the in vivo responses to respiratory toxins in humans.

 

 

 

inhalation services

In vitro Inhalation Services

Vivotecnia can assess a wide range of endpoints using this in vitro human inhalation model:

Mechanism-based assessment:

  • Cell viability (e.g. trypan blue dye exclusion)
  • Cell metabolism (e.g. MTT)
  • Lactate dehydrogenase (LDH) release assay
  • Oxidative stress
  • Inflammation (measuring proinflammatory mediators)
  • Cellular stress responses
  • Tissue damage and matrix degradation
  • Genotoxicity assessment (e.g. DNA damage by comet assay)
  • Gene expression/miRNAs

 

Functional analysis:

    • Airway epithelial tight junction integrity by transepithelial electrical resistance (TEER)
    • Morphology
    • Cilia beating frequency
    • Mucociliary clearance

 

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