Mucosal in Vitro Permeability in the Intestinal Tract of the Pig, the Rat, and Man: Species- and Region-Related Differences

Nejdfors, Pernilla; Ekelund, Mats; Jeppsson, Bengt; Weström, Björn

doi:10.1080/003655200750023769

Cited by 114 publications

(37 citation statements)

References 17 publications

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“…We also assessed for markers that are equally expressed throughout the intestinal tract and found that GATA6, ECAD, and LGR5 were similarly expressed in both groups of organoids [44,45]. The finding that the basal P app of 0.41-0.44 × 10 −7 cm/s of HCOs ( Figure 3B) compares favorably to previous reports using Caco-2 monolayers (0.2-0.5 × 10 −7 cm/s) and human colon (0.1-0.2 × 10 −7 cm/s) recording in Ussing chambers [27,30,33,46]. The 2-2.5 fold decrease in intestinal permeability in colonic epithelium favorably reflects previously published data that show that there is 2-4 fold decrease in permeability in both rat and human explants of small and large intestinal cells ( Figure 2B, Table 1).…”

Section: Discussionsupporting

confidence: 82%

Development of Physiologically Responsive Human iPSC-Derived Intestinal Epithelium to Study Barrier Dysfunction in IBD

Gleeson

Estrada

Yamashita

et al. 2020

IJMS

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In inflammatory bowel disease (IBD), the intestinal epithelium is characterized by increased permeability both in active disease and remission states. The genetic underpinnings of this increased intestinal permeability are largely unstudied, in part due to a lack of appropriate modelling systems. Our aim is to develop an in vitro model of intestinal permeability using induced pluripotent stem cell (iPSC)-derived human intestinal organoids (HIOs) and human colonic organoids (HCOs) to study barrier dysfunction. iPSCs were generated from healthy controls, adult onset IBD, and very early onset IBD (VEO-IBD) patients and differentiated into HIOs and HCOs. EpCAM+ selected cells were seeded onto Transwell inserts and barrier integrity studies were carried out in the presence or absence of pro-inflammatory cytokines TNFα and IFNγ. Quantitative real-time PCR (qRT-PCR), transmission electron microscopy (TEM), and immunofluorescence were used to determine altered tight and adherens junction protein expression or localization. Differentiation to HCO indicated an increased gene expression of CDX2, CD147, and CA2, and increased basal transepithelial electrical resistance compared to HIO. Permeability studies were carried out in HIO- and HCO-derived epithelium, and permeability of FD4 was significantly increased when exposed to TNFα and IFNγ. TEM and immunofluorescence imaging indicated a mislocalization of E-cadherin and ZO-1 in TNFα and IFNγ challenged organoids with a corresponding decrease in mRNA expression. Comparisons between HIO- and HCO-epithelium show a difference in gene expression, electrophysiology, and morphology: both are responsive to TNFα and IFNγ stimulation resulting in enhanced permeability, and changes in tight and adherens junction architecture. This data indicate that iPSC-derived HIOs and HCOs constitute an appropriate physiologically responsive model to study barrier dysfunction and the role of the epithelium in IBD and VEO-IBD.

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Section: Discussionsupporting

confidence: 82%

Development of Physiologically Responsive Human iPSC-Derived Intestinal Epithelium to Study Barrier Dysfunction in IBD

Gleeson

Estrada

Yamashita

et al. 2020

IJMS

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“…Results are in good agreement with those reported for the pig by others [31]–[33], when also including tissue-specific differences between ileum and colon. Overall, our results suggest that subtle but important changes are observed in both ileum and colon in the cases of unprotected anastomosis.…”

Section: Discussionsupporting

confidence: 91%

Bovine Pericardium Patch Wrapping Intestinal Anastomosis Improves Healing Process and Prevents Leakage in a Pig Model

et al. 2014

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Failure of intestinal anastomosis is a major complication following abdominal surgery. Biological materials have been introduced as reinforcement of abdominal wall hernia in contaminated setting. An innovative application of biological patch is its use as reinforcement of gastrointestinal anastomosis. The aim of study was to verify whether the bovine pericardium patch improves the healing of anastomosis, when in vivo wrapping the suture line of pig intestinal anastomosis, avoiding leakage in the event of deliberately incomplete suture. Forty-three pigs were randomly divided: Group 1 (control, n = 14): hand-sewn ileo-ileal and colo-colic anastomosis; Group 2 (n = 14): standard anastomosis wrapped by pericardium bovine patch; Group 3 (n = 1) and 4 (n = 14): one suture was deliberately incomplete and also wrapped by patch in the last one. Intraoperative evaluation, histological, biochemical, tensiometric and electrophysiological studies of intestinal specimens were performed at 48 h, 7 and 90 days after. In groups 2 and 4, no leak, stenosis, abscess, peritonitis, mesh displacement or shrinkage were found and adhesion rate decreased compared to control. Biochemical studies showed mitochondrial function improvement in colic wrapped anastomosis. Tensiometric evaluations suggested that the patch preserves the colic contractility similar to the controls. Electrophysiological results demonstrated that the patch also improves the mucosal function restoring almost normal transport properties. Use of pericardium bovine patch as reinforcement of intestinal anastomosis is safe and effective, significantly improving the healing process. Data of prevention of acute peritonitis and leakage in cases of iatrogenic perforation of anastomoses, covered with patch, is unpublished.

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“…We will focus on the data obtained in humans, laboratory animals, poultry and pigs, as this latter species can be regarded as a good model for man [16,17]. …”

Section: Introductionmentioning

confidence: 99%

Effect of Deoxynivalenol and Other Type B Trichothecenes on the Intestine: A Review

Pinton

Oswald

2014

Toxins

291

240

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The natural food contaminants, mycotoxins, are regarded as an important risk factor for human and animal health, as up to 25% of the world’s crop production may be contaminated. The Fusarium genus produces large quantities of fusariotoxins, among which the trichothecenes are considered as a ubiquitous problem worldwide. The gastrointestinal tract is the first physiological barrier against food contaminants, as well as the first target for these toxicants. An increasing number of studies suggest that intestinal epithelial cells are targets for deoxynivalenol (DON) and other Type B trichothecenes (TCTB). In humans, various adverse digestive symptoms are observed on acute exposure, and in animals, these toxins induce pathological lesions, including necrosis of the intestinal epithelium. They affect the integrity of the intestinal epithelium through alterations in cell morphology and differentiation and in the barrier function. Moreover, DON and TCTB modulate the activity of intestinal epithelium in its role in immune responsiveness. TCTB affect cytokine production by intestinal or immune cells and are supposed to interfere with the cross-talk between epithelial cells and other intestinal immune cells. This review summarizes our current knowledge of the effects of DON and other TCTB on the intestine.

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Mucosal in Vitro Permeability in the Intestinal Tract of the Pig, the Rat, and Man: Species- and Region-Related Differences

Abstract: The results showed differences between intestinal regions and between species. Permeability data from the pig correlated fairly well with those of man, whereas the rat differed, making it difficult to extrapolate from the rat to man.

Cited by 114 publications

References 17 publications

Development of Physiologically Responsive Human iPSC-Derived Intestinal Epithelium to Study Barrier Dysfunction in IBD

Development of Physiologically Responsive Human iPSC-Derived Intestinal Epithelium to Study Barrier Dysfunction in IBD

Bovine Pericardium Patch Wrapping Intestinal Anastomosis Improves Healing Process and Prevents Leakage in a Pig Model

Effect of Deoxynivalenol and Other Type B Trichothecenes on the Intestine: A Review

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