Porcine Ex Vivo Intestinal Segment Model

Ripken, Dina; Hendriks, H.

doi:10.1007/978-3-319-16104-4_23

Cited by 14 publications

(10 citation statements)

References 22 publications

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“…Although it is possible to isolate and culture stem cells from the intestine, most published studies relate to enteroid cultures derived from the small intestine such as duodenum (17), jejunum (13,(18)(19)(20), or ileum (15). Colonoid cultures have been developed from mouse and human, but it is often difficult to obtain human tissue (21). The porcine intestine is a suitable alternative to human intestine because it has greater morphological and functional similarities than that of the mouse and has previously been used by researchers as a model to study intestinal development, disease, and nutrition (22).…”

Section: Introductionmentioning

confidence: 99%

Porcine colonoids and enteroids keep the memory of their origin during regeneration

Barnett

Mullaney

Hendriks

et al. 2021

American Journal of Physiology-Cell Physiology

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The development of alternative in vitro culture methods has increased in the last decade as three-dimensional organoids of various tissues, including those of the small and large intestines. Due to their multicellular composition, organoids offer advantages over traditionally used immortalized or primary cell lines. However, organoids must be accurate models of their tissues of origin. This study compared gene expression profiles with respect to markers of specific cell-types (stem-cells, enterocytes, goblet and enteroendocrine cells) and barrier maturation (tight junctions) of colonoid and enteroid cultures with their tissues of origin, and colonoids with enteroids. Colonoids derived from three healthy pigs formed multi-lobed structures with a monolayer of cells similar to the crypt structures in colonic tissue. Colonoid and enteroid gene expression signatures were more similar to those found for the tissues of their origin than to each other. However, relative to their derived tissues, organoids had increased gene expression levels of stem-cell markers Sox9 and Lgr5 encoding Sex determining region Y-box 9 and leucine-rich repeat-containing G-protein coupled rector 5, respectively. In contrast, expression levels of Occl and Zo1 encoding occludin and zonula occludens 1 respectively, were decreased. Expression levels of the cell lineage markers Atoh1, Cga and Muc2 encoding atonal homolog 1, chromogranin A and mucin 2 respectively, were decreased in colonoids, while Sglt1 and Apn encoding sodium-glucose transporter 1 and aminopeptidase A respectively, were decreased in enteroids. These results indicate colonoid and enteroid cultures were predominantly comprised of undifferentiated cell-types with decreased barrier maturation relative to their tissues of origin.

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Section: Introductionmentioning

confidence: 99%

Porcine colonoids and enteroids keep the memory of their origin during regeneration

Barnett

Mullaney

Hendriks

et al. 2021

American Journal of Physiology-Cell Physiology

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“…Increased extracellular LDH activity is expected after enterocyte plasma membrane damage, mainly when the intestinal tissue is exposed to potentially toxic drugs (34). Thus, LDH is a stable intracellular enzyme that can be readily detected when cell membranes are no longer intact (35,36). Both extracellular and intracellular LDH activities were measured in the current work.…”

Section: Discussionmentioning

confidence: 96%

Plant-Derived Compounds as a Tool for the Control of Gastrointestinal Nematodes: Modulation of Abamectin Pharmacological Action by Carvone

et al. 2020

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The combination of synthetic anthelmintics and bioactive phytochemicals may be a pharmacological tool for improving nematode control in livestock. Carvone (R-CNE) has shown in vitro activity against gastrointestinal nematodes; however, the anthelmintic effect of bioactive phytochemicals either alone or combined with synthetic drugs has been little explored in vivo. Here, the pharmacological interaction of abamectin (ABM) and R-CNE was assessed in vitro and in vivo. The efficacy of this combination was evaluated in lambs naturally infected with resistant gastrointestinal nematodes. Additionally, the ligand and molecular docking of both molecules to P-glycoprotein (P-gp) was studied in silico. The presence of R-CNE produced a significant (p < 0.05) increase of Rho123 and ABM accumulation in the intestinal explants. After 60 min of incubation, Rho123 incubated with R-CNE had a 67 ± 21% higher concentration (p < 0.01) than when it was incubated alone. In the case of ABM, a significant increase in the intestinal concentrations was observed at 15 and 30 min after incubation with R-CNE. In the in vivo assay, no undesirable effects were observed after the oral administration of R-CNE. The coadministration of the natural compound prolonged ABM absorption in lambs. ABM T½ absorption was 1.57-fold longer (p < 0.05) in the coadministered group. Concentrations of R-CNE between 420 and 2,593 ng/mL were detected in the bloodstream between 1 and 48 h posttreatment. The in vivo efficacy of ABM against gastrointestinal nematodes increased from 94.9 to 99.8% in the presence of R-CNE, with the lower confidence interval limit being >90%. In vitro/in vivo pharmacoparasitological studies are relevant for the knowledge of the interactions and the efficacy of bioactive natural products combined with synthetic anthelmintics. While ADMET (absorption, distribution, metabolism, excretion, and toxicity) predictions and the molecular docking study showed a good interaction between ABM and P-gp, R-CNE does not appear to modulate this efflux protein. Therefore, the pharmacokinetic–pharmacodynamic effect of R-CNE on ABM should be attributed to its effect on membrane permeability. The development of pharmacology-based information is critical for the design of successful strategies for the parasite control.

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“…Small circles of tissue segments are punched out and incubated in buffer in 24-wells plates with the test compound. After incubation, the quantity of the test compound absorbed by the intestinal segment is quantified [310]. The intestinal segment model has advantages over the Ussing chamber model in that it is less labour intensive and has a significantly higher throughput [310].…”

Section: Ex Vivo Bioavailability Methodsmentioning

confidence: 99%

Seaweed Components as Potential Modulators of the Gut Microbiota

2021

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Macroalgae, or seaweeds, are a rich source of components which may exert beneficial effects on the mammalian gut microbiota through the enhancement of bacterial diversity and abundance. An imbalance of gut bacteria has been linked to the development of disorders such as inflammatory bowel disease, immunodeficiency, hypertension, type-2-diabetes, obesity, and cancer. This review outlines current knowledge from in vitro and in vivo studies concerning the potential therapeutic application of seaweed-derived polysaccharides, polyphenols and peptides to modulate the gut microbiota through diet. Polysaccharides such as fucoidan, laminarin, alginate, ulvan and porphyran are unique to seaweeds. Several studies have shown their potential to act as prebiotics and to positively modulate the gut microbiota. Prebiotics enhance bacterial populations and often their production of short chain fatty acids, which are the energy source for gastrointestinal epithelial cells, provide protection against pathogens, influence immunomodulation, and induce apoptosis of colon cancer cells. The oral bioaccessibility and bioavailability of seaweed components is also discussed, including the advantages and limitations of static and dynamic in vitro gastrointestinal models versus ex vivo and in vivo methods. Seaweed bioactives show potential for use in prevention and, in some instances, treatment of human disease. However, it is also necessary to confirm these potential, therapeutic effects in large-scale clinical trials. Where possible, we have cited information concerning these trials.

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Porcine Ex Vivo Intestinal Segment Model

Cited by 14 publications

References 22 publications

Porcine colonoids and enteroids keep the memory of their origin during regeneration

Porcine colonoids and enteroids keep the memory of their origin during regeneration

Plant-Derived Compounds as a Tool for the Control of Gastrointestinal Nematodes: Modulation of Abamectin Pharmacological Action by Carvone

Seaweed Components as Potential Modulators of the Gut Microbiota

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