Organotypic Culture Models for Predictive Toxicology Center
The U.S. Environmental Protection Agency (EPA), as part of its Science to Achieve Results (STAR) program, is seeking applications for research centers to investigate toxic effects of chemical substances in three-dimensional (3D) in vitro models, hereafter referred to as Ă‚â€organotypic culture modelsÂ’ (OCMs). OCMs are tissue culture models that mimic in vivo tissue architecture through interactions of heterotypic cell types (e.g., epithelium-stroma) and extracellular matrices (ECM). They can be established from isolated cells or from tissue fragments harvested in vivo, and will bridge the gap between conventional monolayer cell cultures and whole-animal systems. EPA is interested in the potential application of OCMs that mimic complex cell arrangements and physiologies, scalable from mid to higher throughput screening (HTS), and high-content screening (HCS) approaches. This solicitation seeks the formation of research centers that will guide the development and evaluation of OCMs that will accelerate translational research in predictive toxicology. Three dimensional tissue models may, for example, utilize animal cells combined with mechanical scaffolds or microfluidics devices. Under this solicitation, the successful applicant will lead a Center to craft OCMs that can recapitulate critical features of in vivo cellular organization and communication, cell-matrix interplay, morphogenetic processes and differentiation, physiology and chemical metabolism. Measures of success or progress should be described toward the application of OCMs for computational toxicology and reconstructing in vivo responses to environmental chemicals and nanomaterials to improve environmental health protection. As such, the OCMs should be scalable in support of medium to high throughput strategies or high-dimensional quantitative data collection, such as high content imaging, that respond to questions relevant to chemical risk assessment and management. For applications using human cells, it is preferred that the cells are already available or derive from available cell lines. Under EPA Regulation 40 CFR Part 26 (Protection of Human Subjects), using pre-existing human cell lines is not considered human subjects research.
