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EpiIntestinal

1060

Assessing nanotoxicity of food-relevant particles: A comparative analysis of cellular responses in cell monolayers versus 3D gut epithelial cultures

Engineered nanoparticles (NPs) are extensively used in the food industry, yet safety concerns remain. The lack of validated methodologies is a bottleneck towards resolving this uncertainty. Hence, the current study aims to compare two cell models by examining the toxicological impacts of two food-relevant NPs (SiO2 and Ag) on intestinal epithelia using monolayer Caco-2 cells and full-thickness […]
1058

Automated Transepithelial Electrical Resistance (TEER) Measurements Allow for Rapid Screening of the Gastrointestinal Toxicity Profile of Therapeutics

Gastrointestinal toxicity (GIT) ranks among the most common clinical side effects for many orally administered pharmaceuticals, in particular for oncology drugs which are administered over an extended time period. Previously, we utilized an in vitro small intestine (SMI) microphysiological tissue model, EpiIntestinal (Mattek Corporation), which contains the epithelial cell types resident in the native human […]
1056

Novel Approach for Characterizing Exposure and Response to Engineered Nanomaterials in the Gut

Despite the expanding number of applications for engineered nanoparticles (ENP), human health concerns associated with ingested nanoparticles are poorly understood. In this study, we utilized a 3D human small intestinal tissue model to develop a physiologically relevant test system that can assess the toxicological profiles of ingestible nanomaterials. We examined the effects of Cupric (II) […]
1048

SARS-CoV-2 presence in recreational seawater and evaluation of intestine permeability: experimental evidence of low impact on public health

Introduction: Coastal seawater pollution poses a public health risk due to the potential ingestion of contaminated water during recreational activities. Wastewater-based epidemiology has revealed the abundant presence of SARS-CoV-2 in seawater emitted from wastewater outlets. The objective of this research was to investigate the impact of seawater on SARS-CoV-2 infectivity to assess the safety of […]
1047

Tissue-on-a-Chip: Microphysiometry With Human 3D Models on Transwell Inserts

Microphysiometry has proved to be a useful tool for monitoring the energy metabolism of living cells and their interactions with other cells. The technique has mainly been used for monitoring two-dimensional (2D) monolayers of cells. Recently, our group showed that it is also possible to monitor the extracellular acidification rate and transepithelial electrical resistance (TEER) […]
1043

Cytotoxicity and Bioimmunological Activity of Poly(2-Isopropenyl-2- oxazoline) Conjugates with Ibuprofen Using 3D Reconstructed Tissue Models

Poly(2-isopropenyl-2-oxazoline) (PIPOx) represents a universal polymer platform with pendant 2-oxazoline groups, allowing the preparation of biomaterials for various biomedical applications. However, there is a lack of information on PIPOx concerning the effect of molar mass (Mn) on cytotoxicity and bioimmunological properties. Here, aqueous copper(0)-mediated reversible-deactivation radical polymerization (Cu0-RDPR) was used for the preparation of PIPOx […]
1038

A Novel Meso-Scale MPS Integrated Organ Platform to Evaluate Usnic Acid Kinetics, Organ Distribution and Cytotoxicity: A Case Study

Background and Purpose: Usnic acid (UA) is a secondary metabolite obtained from lichens from the genus Usnea. UA has been reported to have a broad range of therapeutic uses that includes anti-inflammatory, antibacterial, and antiviral properties. In addition, UA is used in perfumes and cosmetics. Along with the reported beneficial effects, oral consumption of UA […]
1035

Reconstruction of novel 3D models of the three parts of small intestine for drug toxicity testing

Gastrointestinal (GI) toxicity is a common adverse event that limits pharmaceutical development across diverse therapy areas. The mechanisms of drug induced GI toxicity are often poorly understood, in part due to the lack of physiologically relevant in vitro models that recapitulate the three segments of the small intestine. Traditional in vitro cell cultures utilize the […]
1031

Aichivirus A1 replicates in human intestinal epithelium and bronchial tissue: Lung–gut axis?

The role of aichivirus A1 (AiV-A1) in acute gastroenteritis remains controversial and in vitro data illustrating its pathogenesis in suitable human models are scarce. Here, we demonstrate that AiV-A1 isolate A846/88 replicates in ApoA1- (absorptive) and Ki-67-positive (proliferative) enterocytes in stem cell-derived human small intestinal epithelium (HIE) as well as in patient biopsy samples, but […]
1030

Psilocybin and Eugenol Reduce Inflammation in Human 3D EpiIntestinal Tissue

Inflammation plays a pivotal role in the development and progression of inflammatory bowel disease (IBD), by contributing to tissue damage and exacerbating the immune response. The investigation of serotonin receptor 2A (5-HT2A) ligands and transient receptor potential (TRP) channel ligands is of significant interest due to their potential to modulate key inflammatory pathways, mitigate the […]
1018

In vitro prediction of the performance or equivalence, of different formulations of the same drug substance using a 3D reconstructed human intestinal tissue model: application to generics or drugs in development

“The BCS (Biopharmaceutics Classification System)-based biowaiver approach is intended to reduce the need for in vivo bioequivalence studies in Human, in order to lower costs of development, increase the market access for generic drugs and from an ethical point of view, avoid unnecessary exposure of healthy volunteers (Humans). These waivers are limited to Class I […]
1008

Reconstructed human intestinal comet assay, a possible alternative in vitro model for genotoxicity assessment

The aim of the present study was to evaluate the compatibility of reconstructed 3D human small intestinal microtissues to perform the in vitro comet assay. The comet assay is a common follow-up genotoxicity test to confirm or supplement other genotoxicity data. Technically, it can be performed utilizing a range of in vitro and in vivo […]
998

Modeling of Ligand-Induced Acute and Chronic Inflammation in the gastrointestinal tract using In vitro 3D-human small intestinal microtissues

Intestinal epithelium is known to be involved in innate immune responses by recognizing potential pathogens through cellular pattern recognition receptors (PRRs). The purpose of this study is to investigate PRR responses following exposure of an in vitro 3D human small intestinal (SMI) microtissue to various Toll-like receptor (TLRs) and Node-like receptor (NOD) ligands. The SMI […]
994

Effects of Proteases from Pineapple and Papaya on Protein Digestive Capacity and Gut Microbiota in Healthy C57BL/6 Mice and Dose-Manner Response on Mucosal Permeability in Human Reconstructed Intestinal 3D Tissue Model

Cysteine proteases obtained from the stem of pineapple or papaya latex, bromelain and papain, respectively, exhibit a broad spectrum of beneficial effects on human health. However, their effects on gut microbiota composition or dose manner effects on the intestinal integrity of healthy tissue have not been evaluated. In this study, C57BL/6 young, healthy mice were […]
990

Innovative In Vitro Strategy for Assessing Aluminum Bioavailability in Oral Care Cosmetics

Aluminum is an element found in nature and in cosmetic products. It can interfere with the metabolism of other cations, thus inducing gastrointestinal disorder. In cosmetics, aluminum is used in antiperspirants, lipsticks, and toothpastes. The aim of this work is to investigate aluminum bioavailability after accidental oral ingestion derived from the use of a toothpaste […]
983

Congeners-Specific Intestinal Absorption Of Microcystins In An In Vitro 3D Human Intestinal Epithelium: The Role Of Influx/Efflux Transporters

Microcystins constitute a group of over 200 variants and are increasingly considered as emerging toxins in food and feed safety, particularly with regards to sea-food and fish consumption. Toxicity of MCs is congener-specific, being characterised by different acute potencies, likely related to the differential activity of metabolic enzymes and transporters proteins involved in their cellular […]
969

A Novel Macrophage Containing Organotypic Small Intestinal Tissue for Modeling Gut Inflammation

As gatekeepers of intestinal immunehomeostasis, macrophages play a critical role in inflammation in the gut. In this study, were constructed a new macrophage-containing primary cell-based full-thickness small intestinal(SMI+M) tissue model and characterized it for:1) macrophage incorporation (immunohistochemistry, IHC), 2) barrier properties(TEER), and 3)functionality by measuring inflammatory responses following exposure to ligands for TLR4 (lipopolysaccharide;LPS),NOD1(C12-iE-DAP)andNOD2(L18-MDP) either […]
962

Development of reconstructed intestinal micronucleus cytome (RICyt) assay in 3D human gut model for genotoxicity assessment of orally ingested substances

The micronucleus (MN) assay is widely used as part of a battery of tests applied to evaluate the genotoxic potential of chemicals, including new food additives and novel food ingredients. Micronucleus assays typically utilise homogenous in vitro cell lines which poorly recapitulate the physiology, biochemistry and genomic events in the gut, the site of first […]
949

In vitro models replicating the human intestinal epithelium for absorption and metabolism studies: A systematic review

Absorption, distribution, metabolism and excretion (ADME) studies represent a fundamental step in the early stages of drug discovery. In particular, the absorption of orally administered drugs, which occurs at the intestinal level, has gained attention since poor oral bioavailability often led to failures for new drug approval. In this context, several in vitro preclinical models […]
948

Dietary excess regulates absorption and surface of gut epithelium through intestinal PPARα

Intestinal surface changes in size and function, but what propels these alterations and what are their metabolic consequences is unknown. Here we report that the food amount is a positive determinant of the gut surface area contributing to an increased absorptive function, reversible by reducing daily food. While several upregulated intestinal energetic pathways are dispensable, […]
935

Particulate Matter Decreases Intestinal Barrier-Associated Proteins Levels in 3D Human Intestinal Model

Background: The gastrointestinal tract (GI) tract is one of the main organs exposed to particulate matter (PM) directly through ingestion of contaminated food or indirectly through inhalation. Previous studies have investigated the effects of chronic PM exposure on intestinal epithelia in vitro using Caco−2 cells and in vivo using mice. In this study, we hypothesized […]
928

Multidose evaluation of 6,710 drug repurposing library identifies potent SARS-CoV-2 infection inhibitors In Vitro and In Vivo

The SARS-CoV-2 pandemic has caused widespread illness, loss of life, and socioeconomic disruption that is unlikely to resolve until vaccines are widely adopted, and effective therapeutic treatments become established. Here, a well curated and annotated library of 6710 clinical and preclinical molecules, covering diverse chemical scaffolds and known host targets was evaluated for inhibition of […]
915

Human small intestinal organotypic culture model for drug permeation, inflammation, and toxicity assays

The gastrointestinal tract (GIT), in particular, the small intestine, plays a significant role in food digestion, fluid and electrolyte transport, drug absorption and metabolism, and nutrient uptake. As the longest portion of the GIT, the small intestine also plays a vital role in protecting the host against pathogenic or opportunistic microbial invasion. However, establishing polarized […]
914

Bypassing P-glycoprotein mediated efflux of afatinib by cyclodextrin complexation – Evaluation of intestinal absorption and anti-cancer activity

A cyclodextrin complex of afatinib, a FDA-approved pan–ErbB inhibitor and known P-gp substrate, was developed to enhance its bio-activity while also reducing p-glycoprotein (P-gp) efflux, thereby improving its transport across the intestinal membrane. A sulfobutyl ether derivative of β-cyclodextrin (SBE-β-CD, pharmaceutical grade) was selected based on preliminary phase solubility studies and molecular modeling to prepare […]
888

Fecal Components Modulate Human Astrovirus Infectivity in Cells and Reconstituted Intestinal Tissues

Human astroviruses (HAstV) are among the most common causative agents of viral gastroenteritis, especially in children, and extraintestinal manifestations have also been described. These viruses are transmitted by the fecal-oral route, implying that stool composition and the gut microbiota may impact their ability to remain infectious. For some enteric viruses, individual bacterial envelope components and […]
886

In-Depth Characterization of EpiIntestinal Microtissue as a Model for Intestinal Drug Absorption and Metabolism in Human

The Caco-2 model is a well-accepted in vitro model for the estimation of fraction absorbed in human intestine. Due to the lack of cytochrome P450 3A4 (CYP3A4) activities, Caco-2 model is not suitable for the investigation of intestinal first-pass metabolism. The purpose of this study is to evaluate a new human intestine model, EpiIntestinal microtissues, […]
885

In Search of Preventative Strategies: Novel Anti Inflammatory High-CBD Cannabis Sativa Extracts Modulate ACE2 Expression in COVID-19 Gateway Tissues

With the rapidly growing pandemic of COVID-19 caused by the new and challenging to treat zoonotic SARS-CoV2 coronavirus, there is an urgent need for new therapies and prevention strategies that can help curtail disease spread and reduce mortality. Inhibition of viral entry and thereby spread constitute plausible therapeutic avenues. Similar to other respiratory pathogens, SARS-CoV2 […]
883

In Vitro Demonstration of Intestinal Absorption Mechanisms of Different Sugars Using 3D Organotypic Tissues in a Fluidic Device

Intestinal permeability is crucial in regulating the bioavailability and, consequently, the biological effects of drugs and compounds. However, systematic and quantitative studies of the absorption of molecules are quite limited due to a lack of reliable experimental models able to mimic human in vivo responses. In this work, we present an in vitro perfused model […]
874

Impact of Interleukin-6 on Drug-Metabolizing Enzymes and Transporters in Intestinal Cells

Inflammatory response is characterized by an increase of several cytokines. Some are known to modify drugs pharmacokinetic by reducing the expression levels of drug metabolizing enzymes (DMEs) and transporters. This impact of inflammatory signaling is well established in hepatic cells, but not in intestinal cells. EpiIntestinal is a 3D human small intestinal tissue model with […]
865

A heat-stable microparticle platform for oral micronutrient delivery

Micronutrient deficiencies affect up to 2 billion people and are the leading cause of cognitive and physical disorders in the developing world. Food fortification is effective in treating micronutrient deficiencies; however, its global implementation has been limited by technical challenges in maintaining micronutrient stability during cooking and storage. We hypothesized that polymer-based encapsulation could address […]
855

Behaviour of Silver Nanoparticles in Simulated Saliva and Gastrointestinal Fluids

Continuously increasing application of silver nanoparticles (AgNPs) requires information on their safety and performance under biological conditions. Assessment of AgNPs in biological systems is also related to availability of robust toxicological methods for evaluation of toxic potential of AgNPs and information on their physicochemical state. Silver nanoparticles were subjected to action of simulated saliva, gastric […]
854

Nintedanib-Cyclodextrin Complex to Improve Bio-Activity and Intestinal Permeability

Cyclodextrin complex of nintedanib was prepared aiming for increased bio-activity and improved transport across intestinal membrane with reduced p-glycoprotein (p-gp) efflux. Based on preliminary phase solubility studies and molecular modeling, sulfobutyl ether derivative of β-cyclodextrin (SBE-β-CD, Captisol®) was selected to prepare inclusion complex. Complexation was confirmed using FTIR, 1H NMR, DSC, and XRD. Bioactivity of […]
853

Toxicity of Food Contact Paper Evaluated by Combined Biological and Chemical Methods

The study was focused on assessment of potential health risks of paper-based food contact materials (FCMs) in a step-wise approach using three toxicological bioassays in vitro and chemical analyses of migrating contaminants. 3T3 NRU cytotoxicity test showed high sensitivity to detect basal toxicity of FCMs extracts and served as a firstline test for selection of […]
840

IL-22 Increases Permeability of Intestinal Epithelial Tight Junctions by Enhancing Claudin-2 Expression

Dysfunction of the epithelial barrier is a hallmark of inflammatory intestinal diseases. The intestinal epithelial barrier is maintained by expression of tight junctions that connect adjacent epithelial cells and seal the paracellular space. IL-22 is critical for the maintenance of intestinal barrier function through promoting antipathogen responses and regeneration of epithelial tissues in the gut. However, little is […]
839

Human 3D Gastrointestinal Microtissue Barrier Function As a Predictor of Drug-Induced Diarrhea

Drug-induced gastrointestinal toxicities (GITs) rank among the most common clinical side effects. Preclinical efforts to reduce incidence are limited by inadequate predictivity of in vitro assays. Recent breakthroughs in in vitro culture methods support intestinal stem cell maintenance and continual differentiation into the epithelial cell types resident in the intestine. These diverse cells self-assemble into microtissues with in […]
833

Human Primary Cell-Based Organotypic Microtissues for Modeling Small Intestinal Drug Absorption

Purpose: The study evaluates the use of new in vitro primary human cell-based organotypic small intestinal (SMI) microtissues for predicting intestinal drug absorption and drug-drug interaction. Methods: The microtissues were reconstructed using human intestinal fibroblasts and enterocytes cultured on a permeable support. To evaluate the suitability of the intestinal microtissues to model drug absorption, the permeability coefficients across the microtissues were determined for […]
821

Primary human polarized small intestinal epithelial barriers respond differently to a hazardous and an innocuous protein

An experimental platform employing human-derived intestinal epithelial cell (IEC) line monolayers grown on permeable Transwell® filters was previously investigated to differentiate between hazardous and innocuous proteins. This approach was effective at distinguishing these types of proteins and perturbation of monolayer integrity, particularly transepithelial electrical resistance (TEER), was the most sensitive indicator. In the current report, in vitro indicators of […]
820

Layer-by-Layer Encapsulation of Probiotics for Delivery to the Microbiome

Recent discoveries in biology and microbiology have highlighted the importance of the gastrointestinal (GI) microbiome in regulating human health and disease. Thus, the delivery of probiotics to influence and modulate microbiome compositions can potentially impact the treatment of a number of human diseases. Unfortunately, biological challenges encountered during oral delivery have limited the translation of many probiotic-delivering technologies. Here, we report […]
818

Shigella depends on SepA to destabilize the intestinal epithelial integrity via cofilin activation

Shigella is unique among enteric pathogens, as it invades colonic epithelia through the basolateral pole. Therefore, it has evolved the ability to breach the intestinal epithelial barrier to deploy an arsenal of effector proteins, which permits bacterial invasion and leads to a severe inflammatory response. However, the mechanisms used by Shigella to regulate epithelial barrier permeability remain unknown. To […]
814

Cytotoxicity of copper (II) oxide nanoparticles in rat and human intestinal cell models

Copper (II) oxide nanoparticles (CuO NPs) have a variety of commercial applications ranging from catalysts to semiconductors. There is a potential for human oral exposure to CuO NPs following accidental or intentional ingestion, hand-to-mouth activity, or mucociliary transport following inhalation. CuO NPs are toxic to aquatic organisms but their mammalian toxicity is less well known. […]
810

Health Safety of Food Contact Paper Evaluated by in vitro Toxicological Methods

Paper and paperboard are widely used as food packaging materials intended for direct contact with foodstuffs and have to comply with a basic set of criteria concerning safety. A number of chemicals, such as slimicides, bleaching agents, and inks are used during the paper production process. Consequently, the total amounts of extractables might be high and the […]
798

A four-organ-chip for interconnected long-term co-culture of human intestine, liver, skin and kidney equivalents

Systemic absorption and metabolism of drugs in the small intestine, metabolism by the liver as well as excretion by the kidney are key determinants of efficacy and safety for therapeutic candidates. However, these systemic responses of applied substances lack in most in vitro assays. In this study, a microphysiological system maintaining the functionality of four organs over 28 […]
797

Chip-based human liver–intestine and liver–skin co-cultures – A first step toward systemic repeated dose substance testing in vitro

Systemic repeated dose safety assessment and systemic efficacy evaluation of substances are currently carried out on laboratory animals and in humans due to the lack of predictive alternatives. Relevant international regulations, such as OECD and ICH guidelines, demand long-term testing and oral, dermal, inhalation, and systemic exposure routes for such evaluations. So-called human-on-a-chip concepts are […]
775

SAFETY EVALUATION OF NANOSILVER USING RECONSTRUCTED HUMAN GIT TISSUES

In our pilot study focused on safety evaluation of nanosilver three novel commercially available  reconstructed human  tissues were used for mimicking the human gastrointestinal tract (GIT). The evaluated endpoints included tissue viability, cytokine release and penetration of silver into the tissue culture medium. The results confirmed no adverse effect of nanosilver on the viability of […]
762

ORGANOTYPIC HUMAN SMALL INTESTINAL TISSUE TO ASSESS EPITHELIAL RESTITUTION.

Purpose:  The intestinal epithelium (SMI) forms an important physiological barrier in the gastrointestinal tract but this barrier can be compromised by a wide range of substances including drugs, microbes, and dietary substances traveling through the lumen.  Since repeated epithelial damage or injury are implicated in intestinal disorders including inflammatory bowel diseases, rapid closure or resealing […]
763

NOVEL 3D HUMAN SMALL INTESTINAL TISSUE MODEL (EPIINESTINAL™ ) TO ASSESS DRUG PERMEATION & INFLAMMATION

Purpose:  Drug transport and permeability across the small intestine (SMI) is a key parameter for determining bioavailability of orally administered drugs. The currently available in vitro models are highly dependent on immortalized cell lines (e.g. Caco-2) and have significant deficiencies for drug development applications. Therefore, we developed an in vitro SMI model (EpiIntestinalTM) using normal […]
750

RECONSTRUCTION OF NEW ORGANOTYPIC 3D HUMAN SMALL INTESTINE TISSUE MODEL FOR DRUG SAFETY AND TOXICITY.

The epithelial lining of the gastrointestinal (GI) tract is a gatekeeper for entry of orally ingested nutrients and xenobiotics including medicaments. The small intestine has a well organized structure containing proliferative cells which migrate along the crypt-villi axis and differentiate into functionally mature epithelial cells. Currently, the most common in vitro model utilized for study […]
779

The impact of dietary fibers on dendritic cell responses in vitro is dependent on the differential effects of the fibers on intestinal epithelial cells

SCOPE: In the present study, the direct interaction of commonly consumed fibers with epithelial or dendritic cells (DCs) was studied. METHODS AND RESULTS: The fibers were characterized for their sugar composition and chain length profile. When in direct contact, fibers activate DCs only mildly. This was different when DCs and fibers were co-cultured together with […]