Study Transportation of Drugs within Newly Established Murine Colon Organoid Systems.

Autor: Davoudi Z; Department of Chemical and Biological Engineering, Iowa State University, Ames, IA, 50014, USA., Atherly T; Department of Veterinary Clinical Sciences, Iowa State University, Ames, IA, 50014, USA., Borcherding DC; Department of Biomedical Sciences, Iowa State University, Ames, IA, 50014, USA., Jergens AE; Department of Veterinary Clinical Sciences, Iowa State University, Ames, IA, 50014, USA., Wannemuehler M; Department of Vet Microbiology and Preventive Medicine, Iowa State University, Ames, IA, 50014, USA., Barrett TA; Department of Internal Medicine, Division of Gastroenterology, University of Kentucky, Lexington, KY, 40536, USA., Wang Q; Department of Chemical and Biological Engineering, Iowa State University, Ames, IA, 50014, USA.
Jazyk: angličtina
Zdroj: Advanced biology [Adv Biol (Weinh)] 2023 Dec; Vol. 7 (12), pp. e2300103. Date of Electronic Publication: 2023 Aug 21.
DOI: 10.1002/adbi.202300103
Abstrakt: The development of 3D organoids of the small intestine is a tremendous breakthrough in drug development and biological research. However, the development of colonic organoids (i.e., colonoids) is particularly challenging due to a lack of simple, cost-effective protocols for colonoid cultivation. Here, intestinal homogenates are described as a supplement to the culture medium for maintaining and replicating colonic stem cells. Colonoids generated by this cultivation protocol demonstrate substantial proliferation and differentiation (3 months). There is a similarity between cultured colonoids and primary colon tissue regarding structure and functionality. To evaluate the functionality of colonoids, permeability testing is performed with suspensions of 4 and 40 kDa fluorescein isothiocyanate-dextran (FITC-DEX). It is observed that neither can permeate the healthy epithelial barrier. The P-glycoprotein receptor, a vital drug efflux pump mitigating potential drug toxicity, is functionally manipulated, as evidenced by its inhibition function by verapamil and monitoring uptake of Rhodamin 123. In addition, Forskolin treatment which affects chloride transport results in organoid swelling; this confirms the functional expression of the CFTR transporter in the colonoids. This protocol to generate colonoids is promising for high-throughput drug screening, toxicity testing, and oral drug development.
(© 2023 The Authors. Advanced Biology published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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