Cell culture system that acts as an in vitro model for infection and stress-induced airway inflammation; used for research and drug discovery/screening.
- Improved structure of system offers natural path for neutrophil transepithelial migration, unlike current systems.
- More accurately models pathological environment due to integration of airway fluid from patients.
- Could be used to model other tissues (e.g. gut) beyond small airways.
Human small airway epithelial cells (SAECs) are a subset of general respiratory epithelial cells isolated from normal human lung tissue in the distal portion of the lung (bronchioles). These cells are a prime target for bacterial and viral infection, can be subjected to environmental damage, and may recruit blood leukocytes to initiate an inflammatory response. Research into how SAECs orchestrate inflammation in reaction to various stressors has been a challenge due to a lack of a good in vitro model for how the cells function in their native system and interact with leukocytes. Current models are unable to mimic these properties found in small airways adequately, even though they are used for drug screening and development for small airway diseases, such as cystic fibrosis (CF), asthma, non-CF bronchiectasis, viral bronchiolitis and chronic obstructive pulmonary disease (COPD).
Emory researchers have developed an improved system for leukocyte transmigration that models airway tissue by using a honeycomb structure topped with two biological barriers instead of the pre-drilled holes or channels of current systems. This honeycomb structure allows leukocytes to migrate up through the layer in any direction, similar to the way they normally would in vivo. To cross into the lumen, leukocytes also have to actively crawl through a collagen layer and a tight epithelium, also similar to in vivo. Overall, the culture system better recapitulates the complex relationship between small airway epithelial cells and leukocytes. The system is highly customizable as the source of leukocytes, the genetically-altered SAEC layer, and the patient-derived or synthetic apical fluid with or without pathogens and/or candidate drugs can be changed. In its first iteration, the system has been customized to recapitulate the pathological conditions found in cystic fibrosis (CF). Other applications of the model include asthma, non-CF bronchiectasis, viral bronchiolitis and chronic obstructive pulmonary disease (COPD). The cell culture system can be used as a research tool to study the impacts of stressors upon a disease and small airways as well as for drug discovery, screening, and development purposes.
- Cell culture system available and being used for drug screening in the lab.
- Cell culture has been used to support drug development for the biotech industry.