Human and rat precision-cut intestinal slices as ex vivo models to study bile acid uptake by the apical sodium-dependent bile acid transporter

Li, Ming; Vokřál, Ivan; Evers, Bernard; Graaf, Inge A. M. de; Jager, Marina H. de; Groothuis, Geny M. M.

doi:10.1016/j.ejps.2018.05.005

Cited by 9 publications

(8 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…90,91 Since these samples come directly from a living organism, the proportions of cell types, ECM composition, and tissue structure are all physiological, making explants an attractive platform to study complex aspects of intestinal biology, such as inflammatory intestinal diseases, drug toxicity and interactions, and the transport of nutrients, bile-acids, and drugs. [91][92][93] It can be generally challenging to obtain human samples and more or less impossible to control factors that influence intestinal biology, such as diet. Another drawback to using explants is the limited survival time, which is usually around 48 h. 94 The Ussing chamber is a popular apparatus for measuring barrier function in explants.…”

Section: Explantsmentioning

confidence: 99%

In VitroModels of the Small Intestine: Engineering Challenges and Engineering Solutions

Hewes

Wilson

Estes

et al. 2020

Tissue Engineering Part B: Reviews

View full text Add to dashboard Cite

Pathologies affecting the small intestine contribute significantly to the disease burden of both the developing and the developed world, which has motivated investigation into the disease mechanisms through in vitro models. Although existing in vitro models recapitulate selected features of the intestine, various important aspects have often been isolated or omitted due to the anatomical and physiological complexity. The small intestine's intricate microanatomy, heterogeneous cell populations, steep oxygen gradients, microbiota, and intestinal wall contractions are often not included in in vitro experimental models of the small intestine, despite their importance in both intestinal biology and pathology. Known and unknown interdependencies between various physiological aspects necessitate more complex in vitro models. Microfluidic technology has made it possible to mimic the dynamic mechanical environment, signaling gradients, and other important aspects of small intestinal biology. This review presents an overview of the complexity of small intestinal anatomy and bioengineered models that recapitulate some of these physiological aspects. Keywords: gut-on-a-chip, microfluidic models of intestine, small intestine model, tissue engineered intestine Impact Statement There is a need for improved cell culture models of the small intestine. To develop such models, it is necessary to give engineers a better understanding of intestinal biology, and conversely, to give biologists an idea of what is possible with microfluidic devices and biomaterial platforms. This work provides a detailed overview of aspects of intestinal biology that are important for tissue engineers to understand when designing models of the small intestine and provides a summary of current approaches. This review highlights both unique and common features of various strategies for modeling the intestinal cell environment, not only using microfluidic chip-based systems but also several elegant designs that use a materials-based static culture approach.

show abstract

Section: Explantsmentioning

confidence: 99%

In VitroModels of the Small Intestine: Engineering Challenges and Engineering Solutions

Hewes

Wilson

Estes

et al. 2020

Tissue Engineering Part B: Reviews

View full text Add to dashboard Cite

show abstract

“…The robust drug‐metabolizing enzyme activity is a major advantage of CHIM over crypt cell/stem cell‐derived and cell line‐based in vitro enteric models 61 . The overall results suggest that CHIM represents a convenient and effective 3D in vitro experimental model, which, together with results obtained with other metabolically competent enteric models, including human intestinal slices, 62,63 cryopreserved human enterocytes 64 and permeabilized, cofactor‐supplemented (MetMax) cryopreserved human enterocytes 65 can be used for the assessment of human enteric drug properties, including drug metabolism, DDIs, and drug toxicity. Future developments with CHIM include the establishment of experimental approaches for the evaluation of transporter‐mediated efflux and uptake, which are mainly evaluated with cell lines, such as Caco2 cells that are deficient in drug metabolizing enzyme activities 66 …”

Section: D In Vitro Intestine Modelsmentioning

confidence: 90%

3D cell culture models: Drug pharmacokinetics, safety assessment, and regulatory consideration

Wang

Brown

Chow

et al. 2021

Clinical Translational Sci

120

View full text Add to dashboard Cite

sclerosis (ALS), cystic fibrosis conductance regulator (CFTR), cryopreserved human intestinal mucosal epithelium (CHIM), cystic fibrosis (CF), drug-drug interactions (DDIs), drug-induced liver injury (DILI), high-throughput screening (HTS), human liver microtissues (hLiMTs), long noncoding RNAs (lncRNAs), margin of safety (MOS), micropatterned co-culture (MPCC), microphysiological systems (MPS), model-informed drug development (MIDD), neuromuscular junction (NMJ), nonparenchymal cell (NPC), patient-derived tumor organoid (PDTO), pharmacokinetics (PK), physiologically based pharmacokinetic (PBPK), three-dimensional (3D), Toll-like receptor 2 (TLR2)

show abstract

“…However pre-exposure to 2 μM DON decreased the amount of TCA transported across the Caco-2 cell layers. TCA has long been used as a model bile acid for the study of bile acid active transport (Heubi et al 1982 ; Li et al 2018 ). In vivo, decreased bile acid active transport may lead to disturbance of bile acid homeostasis, as most of the bile acid pool in human intestine is conjugated to taurine or glycine metabolites.…”

Section: Discussionmentioning

confidence: 99%

“…The ileal ASBT mediates the initial uptake of bile acids across the ileal enterocyte apical brush border membrane, only a small fraction of the taurine or glycine bile acid metabolites escapes absorption and is excreted in the feces (Li et al 2018 ). In our study, the mRNA expression of ASBT was decreased following DON exposure.…”

Section: Discussionmentioning

confidence: 99%

Exposure to the mycotoxin deoxynivalenol reduces the transport of conjugated bile acids by intestinal Caco-2 cells

et al. 2022

View full text Add to dashboard Cite

Conjugated bile acids are synthesized in liver and subsequently secreted into the intestinal lumen from which they are actively reabsorbed and transported back to liver. The efficient enterohepatic circulation of conjugated bile acids is important to maintain homeostasis. The mycotoxin deoxynivalenol (DON) is a fungal secondary metabolite that contaminates cereal food. Upon human exposure, it can cause intestinal dysfunction. We explored the effects of DON exposure on the intestinal absorption of conjugated bile acids and the expression of bile acid transporters using an in vitro model based on Caco-2 cell layers grown in transwells. Our study shows that the transport rate of taurocholic acid (TCA) is decreased after 48-h pre-exposure of the Caco-2 cells to 2 µM DON, which is a realistic intestinal DON concentration. Exposure to DON downregulates expression of the genes coding for the apical sodium-dependent bile acid transporter (ASBT), the ileal bile acid-binding protein (IBABP) and the organic solute transporter α (OSTα), and it counteracts the agonist activity of Farnesoid X receptor (FXR) agonist GW4064 on these genes. In addition, the transport of ten taurine or glycine-conjugated bile acids in a physiological relevant mixture by the intestinal Caco-2 cell layers was decreased after pre-exposure of the cells to DON, pointing at a potential for DON-mediated accumulation of the conjugated bile acids at the intestinal luminal side. Together the results reveal that DON inhibits intestinal bile acid reabsorption by reducing the expression of bile acid transporters thereby affecting bile acid intestinal kinetics, leading to bile acid malabsorption in the intestine. Our study provides new insights into the hazards of DON exposure.

show abstract

Human and rat precision-cut intestinal slices as ex vivo models to study bile acid uptake by the apical sodium-dependent bile acid transporter

Abstract: 2018). Human and rat precision-cut intestinal slices as ex vivo models to study bile acid uptake by the apical sodiumdependent bile acid transporter.

Cited by 9 publications

References 50 publications

In VitroModels of the Small Intestine: Engineering Challenges and Engineering Solutions

In VitroModels of the Small Intestine: Engineering Challenges and Engineering Solutions

3D cell culture models: Drug pharmacokinetics, safety assessment, and regulatory consideration

Exposure to the mycotoxin deoxynivalenol reduces the transport of conjugated bile acids by intestinal Caco-2 cells

Contact Info

Product

Resources

About