1. Bioprinted 3D Primary Human Intestinal Tissues Model Aspects of Native Physiology and ADME/Tox Functions
- Author
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Theresa V. Nguyen, Salvador Garcia-Mojica, Alex V. Le, Andrea M. Peier, Lauran R. Madden, Vishal D. Shah, Sharon C. Presnell, Kelsey N. Retting, Eric M. Parker, Deborah G. Nguyen, and Richard Visconti
- Subjects
0301 basic medicine ,Multidisciplinary ,Tight junction ,02 engineering and technology ,Biology ,021001 nanoscience & nanotechnology ,Epithelium ,Cell biology ,03 medical and health sciences ,030104 developmental biology ,medicine.anatomical_structure ,Intestinal mucosa ,Tissue engineering ,Drug development ,medicine ,Specialized Epithelial Cell ,lcsh:Q ,0210 nano-technology ,lcsh:Science ,Barrier function ,ADME - Abstract
Summary: The human intestinal mucosa is a critical site for absorption, distribution, metabolism, and excretion (ADME)/Tox studies in drug development and is difficult to recapitulate in vitro. Using bioprinting, we generated three-dimensional (3D) intestinal tissue composed of human primary intestinal epithelial cells and myofibroblasts with architecture and function to model the native intestine. The 3D intestinal tissue demonstrates a polarized epithelium with tight junctions and specialized epithelial cell types and expresses functional and inducible CYP450 enzymes. The 3D intestinal tissues develop physiological barrier function, distinguish between high- and low-permeability compounds, and have functional P-gp and BCRP transporters. Biochemical and histological characterization demonstrate that 3D intestinal tissues can generate an injury response to compound-induced toxicity and inflammation. This model is compatible with existing preclinical assays and may be implemented as an additional bridge to clinical trials by enhancing safety and efficacy prediction in drug development. : In Vitro Toxicology Including 3D Culture; Bioengineering; Tissue Engineering Subject Areas: In Vitro Toxicology Including 3D Culture, Bioengineering, Tissue Engineering
- Published
- 2018