2. Academic Validation
  3. Characterization of in vitro Mrp2 transporter model based on intestinal organoids

Characterization of in vitro Mrp2 transporter model based on intestinal organoids

  • Regul Toxicol Pharmacol. 2019 Nov;108:104449. doi: 10.1016/j.yrtph.2019.104449.
Lei Zhang 1,  Chenmeizi Liang 2,  Peipei Xu 2,  Mingyao Liu 3,  Feng Xu 4,  Xin Wang 5
Affiliations

Affiliations

  • 1 East China Normal University and Shanghai Fengxian District Central Hospital Joint Research Center for Translational Medicine, Shanghai Key laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China; Department of Pharmacy, Shanghai Fengxian District Central Hospital, Shanghai, China.
  • 2 East China Normal University and Shanghai Fengxian District Central Hospital Joint Research Center for Translational Medicine, Shanghai Key laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
  • 3 East China Normal University and Shanghai Fengxian District Central Hospital Joint Research Center for Translational Medicine, Shanghai Key laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China; Department of Molecular and Cellular Medicine, Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, TX, USA.
  • 4 East China Normal University and Shanghai Fengxian District Central Hospital Joint Research Center for Translational Medicine, Shanghai Key laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China; Department of Pharmacy, Shanghai Fengxian District Central Hospital, Shanghai, China. Electronic address: [email protected].
  • 5 East China Normal University and Shanghai Fengxian District Central Hospital Joint Research Center for Translational Medicine, Shanghai Key laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China. Electronic address: [email protected].
PMID: 31449916 DOI: 10.1016/j.yrtph.2019.104449
Abstract

Multidrug resistance associated protein 2 (MRP2) is an important efflux transporter involved in clinical drug disposition and drug-drug interactions. The study of MRP2-mediated drug transport has become an integral part of drug discovery and development. In particular, screening of specific MRP2 inhibitors will help overcome the multidrug resistance in Cancer. In this report, a new method for rapid and sensitive detection of Mrp2 function was established via using mouse small intestinal organoids. Firstly, small intestinal crypts isolated from mouse intestine were induced by Noggin, R-spondin1 and EGF to develop three-dimensional (3D) organoids. Secondly, the 3D organoids were characterized by the physical and physiological structure of Mrp2-mediated drug transport. Finally, Mrp2 fluorescent substrate 5(6)-carboxyl- 2', 7'-dichlorofluorescein (CDF) and its inhibitor MK-571 and probenecid were used to demonstrate Mrp2-mediated CDF transport in 3D organoids. The results showed that the small intestinal organoids have a physiological structure for Mrp2-mediated compound transport. Moreover, MK-571 and probenecid, inhibitors of MRP2, significantly decreased the accumulation of CDF in 3D organoids. In summary, a novel intestinal organoid model has been successfully established for the rapid and effective study of Mrp2-mediated drug transport.

Keywords

Drug transport; Intestinal organoids; Mouse; Multidrug resistance-associated protein 2 (Mrp2); Transporter model.

Figures
Products