Determining The Fundamental Differences Among Tissue Organoids From Different Species For Modeling The Effects Of Biochemical Warfare Agents And Developing Effective Countermeasures
Abstract
Three-dimensional cell culture systems containing human are beginning to show great promise in modeling the way human tissue process and respond to drugs. Our team has made significant advances in better modeling the environmental conditions of normal tissue within these three dimensional models. This has resulted in increased stability, and higher fidelity modeling of how drugs are processed in human tissue and how human tissue responds to drugs. The tissue environment factors that our team has included in the three dimensional cell models are 1) including all of the different cell types found in normal tissue 2) tuning the stiffness of the model to match the stiffness of human tissue, and 3) including the thin layer of connecting tissue between cells that glue them together and provide a normal "home" for the cells to live in. We propose building three dimensional cell models for liver, lung and intestine from cells derived from various research animal species. Our group will test these models to prove that the known interspecies differences in drug processing and drug effects are accurately represented in these models. The results would be used to show that our three dimensional cell systems would be useful for a variety of applications including: 1) Scientists could use these cell models to screen potential drugs and antidotes to help choose a species of research animal that most accurately mimics the way the compound will be processed in humans. 2) Experiments for developing new drugs and antidotes could be performed directly in these cell models, limiting the number of research animals that would need to be used. 3) Validation of these three dimensional cell models would continue to build confidence in this technology within the FDA, USDA, NIST, EPA, and other regulatory agencies.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Aug 01, 2019
- Source ID
- HDTRA11910013
Entities
People
- Anthony Atala
Organizations
- Agent Blue
- Defense Threat Reduction Agency