New laboratory tool may more accurately predict human response to respiratory challenges and therapeutics
RESEARCH TRIANGLE PARK, N.C. — RTI International was recently awarded funding to develop a 3-D in vitro cell culture that closely emulates the human lung. The technology, called the fluidic-enhanced airway model, will provide a unique capability by reproducing the human response to respiratory challenges and pharmaceuticals in a laboratory.
Funded by a $3.8 million contract from the Defense Threat Reduction Agency (DTRA), the technology is being developed in collaboration with the University of North Carolina at Chapel Hill.
"We are grateful for the opportunity provided by the DTRA award," said Sonia Grego, Ph.D., a research scientist at RTI and the project principal investigator. "I believe this technology has great potential to provide rapid and accurate predictions of human response to respiratory infections and drugs."
The respiratory system is a prime site of exposure to natural and bioengineered pathogens, as well as an attractive drug delivery route. Currently, therapeutic treatments are investigated using conventional cell culture assays and animal models. Despite these time-consuming preclinical studies, treatments often fail in human clinical trials.
The technology employs primary human lung cells in an engineered fluidic chip, enabling a sophisticated culture of multiple cell types that closely mimics the morphology and physiology of the human lung—essentially an "organ-on-a-chip." The use of human cell cultures avoids the heterogeneity of tissue slice studies and uncertainties related to species-specific responses of animal models.
DTRA's Chemical and Biological Technologies Directorate functions as the Joint Science and Technology Office for Chemical and Biological Defense. Its purpose is to develop scientific knowledge and technical solutions to reduce the chemical and biological threat to the military and the nation.
The technology is being developed as an in vitro platform of a human organ construct that can accurately predict human safety, efficacy and pharmacokinetics of candidate medical countermeasures (i.e., therapeutics and pharmaceuticals). It is envisioned that such a platform could be used in the development of medical countermeasures by generating data to support in vivo testing and evaluation plans for investigational therapeutics. A long-term goal of this research is to reduce the overall burden of in vivo testing in the development and management of drugs and products for human use.
The project team includes Brian Gilmour, Ph.D., a research pharmacologist at RTI, and Scott Randell, Ph.D., and Ralph Baric, Ph.D., from the University of North Carolina at Chapel Hill.
RTI is also working on an in vitro heart model for studies of drug cardiac toxicity, a major concern in drug development and a leading cause of drug withdrawal from clinical studies.
The Defense Threat Reduction Agency (DTRA) safeguards America's interests from weapons of mass destruction (chemical, biological, radiological, nuclear and high explosives) by controlling and reducing the threat to the United States and its allies, and providing quality tools and services for the warfighter. This Department of Defense combat support agency is located on Fort Belvoir, Va., and operates field offices worldwide.