A Pre-clinical Model to Evaluate Therapeutics for Respiratory Infections
The current COVID-19 pandemic has highlighted the need for a robust pre-clinical model of the respiratory tract that can allow researchers to accurately and efficiently test potential therapeutic agents against emergent infections like SARS-CoV-2. Influenza and coronaviruses like SARS-CoV-2 utilize the lung and airway cells of the respiratory tract as the main entry point into the body. The authors of a recent publication utilized Lifeline’s Human Bronchial/Tracheal Epithelial Cells (HBTECs) to develop a new high throughput in vitro model with better physiological relevance than current systems that could help expedite timelines to test lifesaving therapeutics.
In addition to HBTECs, Lifeline offers a number of other healthy and diseased state lung and airway cells as well as optimized BronchiaLife™ cell culture media. Click on the links below for more information:
- Small airway cells
- Diseased small airway epithelial cells – asthma and COPD
- Bronchial/tracheal epithelial cells
- Diseased bronchial/tracheal epithelial cells – cystic fibrosis
- Bronchial/tracheal smooth muscle cells
- Lobar bronchial epithelial cells
- Lung fibroblasts
- Lung smooth muscle cells
- Laryngeal epithelial cells
- BronchiaLife Complete Medium Kit
PREDICT96-ALI Model Developed with Lifeline’s Bronchial/Tracheal Epithelial Cells
Currently, pre-clinical studies used to test therapeutics for respiratory tract infections utilize high-throughput, low-fidelity in vitro screening with human cell lines and/or low-throughput animal models, both of which are often poorly correlated to human clinical responses resulting in a large percentage of drug failures in clinical trials that extend timelines to finding a successful drug candidate. Here, we summarize research by Gard and Colleagues where they successfully developed a high throughput in vitro human primary airway epithelial cell-based model on the PREDICT96-ALI microfluidics platform that is better able to accurately predict clinical responses compared to traditional screening methods.
Lifeline’s primary HBTECs were cultured in our BronchiaLife media and then differentiated using the HBTEC-ALI differentiation media to create a pseudostratified epithelium at an air-liquid interface (ALI) in the PREDICT96-ALI platform. The polarity of the cells at the ALI is a suitable analogue of in vivo respiratory barrier tissues mimicking a range of physiologically relevant responses. The authors used the healthy baseline airway model to test the system’s permissiveness and response to viral infections using three different strains of Influenza A (IAV), the A/WSN/33 strain, and pandemic strains of H1N1 and H3N2. Infection kinetics were determined using immunofluorescence (IF) and qPCR across a range of multiplicities of infection (MOIs) and time points. And, as a proof-of-concept, viral infection kinetics for a single IAV strain in response to pre-treatment of the airway cells with an antiviral (oseltamivir) was investigated to determine if the system could qualify the efficacy of novel therapeutic compounds.
Airway cells in the PREDICT96-ALI model were shown to be permissive to viral infection as determined by IF and qPCR results where a dose-dependent increase of viral protein and RNA, respectively, is observed as MOI increased from 0.1 – 10. To evaluate the efficacy of the model to test therapeutic agents, the airway cells were treated with the antiviral oseltamivir (Tamiflu) for 2 hrs before viral inoculation (A/WSN/33 H1N1 virus) at various MOIs. Oseltamivir treatment in the PREDICT96-ALI airway model significantly reduced influenza replication, maintained barrier integrity, and had viral copy numbers comparable to those observed in a clinical setting with patients.
Taken together, these promising results demonstrate the permissiveness to infection and the potential of the PREDICT96-ALI airway model as a pre-clinical tool to evaluate potential therapies for combating respiratory infections including SARS-CoV-2 in an efficient, robust, and high-throughput manner. Additionally, compatibility with existing pharmaceutical laboratory infrastructure, convenient readouts for quality control and physiological monitoring, makes this platform suitable across many disease areas and application domains over other micro-physiological systems (MPS). The development of more accurate viral testing systems will undoubtedly aide researchers to screen potential drug treatments faster than ever before.
Tune in for the next installation of our blog featuring new research using Lifeline products and industry highlights. If you have used Lifeline products to further your research, we would love to hear from you.