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Bioprinted 3D Primary Human Intestinal Tissues Model Aspects of Native Physiology and ADME/Tox Functions.
Madden, Lauran R; Nguyen, Theresa V; Garcia-Mojica, Salvador; Shah, Vishal; Le, Alex V; Peier, Andrea; Visconti, Richard; Parker, Eric M; Presnell, Sharon C; Nguyen, Deborah G; Retting, Kelsey N.
Afiliación
  • Madden LR; Organovo, Inc., San Diego, CA 92121, USA.
  • Nguyen TV; Department of Pharmacokinetics, Merck & Co., Inc., Rahway, NJ 07065, USA.
  • Garcia-Mojica S; Organovo, Inc., San Diego, CA 92121, USA.
  • Shah V; Organovo, Inc., San Diego, CA 92121, USA.
  • Le AV; Organovo, Inc., San Diego, CA 92121, USA.
  • Peier A; Department of Pharmacology, Merck & Co., Inc., Kenilworth, NJ 07033, USA.
  • Visconti R; Department of Pharmacology, Merck & Co., Inc., Kenilworth, NJ 07033, USA.
  • Parker EM; Department of Pharmacology, Merck & Co., Inc., Kenilworth, NJ 07033, USA.
  • Presnell SC; Organovo, Inc., San Diego, CA 92121, USA.
  • Nguyen DG; Organovo, Inc., San Diego, CA 92121, USA.
  • Retting KN; Organovo, Inc., San Diego, CA 92121, USA. Electronic address: kretting@organovo.com.
iScience ; 2: 156-167, 2018 Apr 27.
Article en En | MEDLINE | ID: mdl-30428372
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: IScience Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: IScience Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos