Implementation of a dynamic intestinal gut-on-a-chip barrier model for transport studies of lipophilic dioxin congeners

Kulthong, Kornphimol; Duivenvoorde, Loes P. M.; Mizera, Barbara Z.; Rijkers, Deborah; Dam, Guillaume ten; Oegema, Gerlof; Puzyn, Tomasz; Bouwmeester, Hans; Zande, Meike van der

doi:10.1039/c8ra05430d

Cited by 39 publications

(41 citation statements)

References 71 publications

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“…No other studies on the effects of shear www.nature.com/scientificreports/ www.nature.com/scientificreports/ forces on Caco-2 cells based on transcriptomics data could be found. As reported previously, cells grown under dynamic conditions seemed to be larger compared to cells grown under static conditions 12,13 . The morphology of Caco-2 cells has been shown to be affected by differences in shear forces.…”

Section: Discussionsupporting

confidence: 84%

“…Design of the gut-on-chip system. The microfluidic gut-on-chip device has been developed and described previously 12,13 . Briefly, the chip consists of three 15 × 45 mm (width x length) re-sealable glass slides that result in two flow chambers (i.e.…”

Section: Discussionmentioning

confidence: 99%

“…Cell culture. The cell culture was performed using a protocol described previously in our studies 12,13 . A Caco-2 cell line (HTB-37), derived from a human colorectal adenocarcinoma (ATCC, Manassas, VA, USA), were grown (at passage number [29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45] in DMEM supplemented with 1% penicillin/streptomycin, 1% MEM non-essential amino acid and 10% FBS, further indicated as DMEM + .…”

Section: Methodsmentioning

confidence: 99%

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Transcriptome comparisons of in vitro intestinal epithelia grown under static and microfluidic gut-on-chip conditions with in vivo human epithelia

Kulthong

Hooiveld

Duivenvoorde

et al. 2021

Sci Rep

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Gut-on-chip devices enable exposure of cells to a continuous flow of culture medium, inducing shear stresses and could thus better recapitulate the in vivo human intestinal environment in an in vitro epithelial model compared to static culture methods. We aimed to study if dynamic culture conditions affect the gene expression of Caco-2 cells cultured statically or dynamically in a gut-on-chip device and how these gene expression patterns compared to that of intestinal segments in vivo. For this we applied whole genome transcriptomics. Dynamic culture conditions led to a total of 5927 differentially expressed genes (3280 upregulated and 2647 downregulated genes) compared to static culture conditions. Gene set enrichment analysis revealed upregulated pathways associated with the immune system, signal transduction and cell growth and death, and downregulated pathways associated with drug metabolism, compound digestion and absorption under dynamic culture conditions. Comparison of the in vitro gene expression data with transcriptome profiles of human in vivo duodenum, jejunum, ileum and colon tissue samples showed similarities in gene expression profiles with intestinal segments. It is concluded that both the static and the dynamic gut-on-chip model are suitable to study human intestinal epithelial responses as an alternative for animal models.

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Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Transcriptome comparisons of in vitro intestinal epithelia grown under static and microfluidic gut-on-chip conditions with in vivo human epithelia

Kulthong

Hooiveld

Duivenvoorde

et al. 2021

Sci Rep

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“…The first-generation microscale cell culture analog (μCCA) devices mimicking the organ-level function of human physiology were fabricated on silicon ( Sin et al, 2004 ; Mahler et al, 2009 ). Compared to opaque silicon, glass is optically transparent and optimal for real-time imaging, while reducing the absorbance of hydrophobic molecules and the adsorption of biomolecules ( Lee S. et al, 2017 ; Kulthong et al, 2018 ). Nevertheless, glass chips with enclosed channels are not suitable for long-term cell culture because glass is not gas permeable.…”

Section: Materials For Oocsmentioning

confidence: 99%

Biomedical Application of Functional Materials in Organ-on-a-Chip

Ding

Chen

Kang

et al. 2020

Front. Bioeng. Biotechnol.

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The organ-on-a-chip (OOC) technology has been utilized in a lot of biomedical fields such as fundamental physiological and pharmacological researches. Various materials have been introduced in OOC and can be broadly classified into inorganic, organic, and hybrid materials. Although PDMS continues to be the preferred material for laboratory research, materials for OOC are constantly evolving and progressing, and have promoted the development of OOC. This mini review provides a summary of the various type of materials for OOC systems, focusing on the progress of materials and related fabrication technologies within the last 5 years. The advantages and drawbacks of these materials in particular applications are discussed. In addition, future perspectives and challenges are also discussed.

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“…As shown in Table 1, the apparent permeability coefficients observed in our study corresponds with the range of data found in the literature. Comparison of our dynamic automated system with other dynamic systems is challenging as there is a high variety in designs and there are only a limited number of studies examining the absorptive capacity of the model [10,14,20,40,41]. For a widespread use of dynamic in vitro intestinal barrier models and incorporation of them in drug development trials and risk assessment approaches, more permeability data of model compounds needs to be generated using the dynamic devices, including benchmarking against the static Transwell and in vivo data.…”

Section: Temporal Analysis Of Intestinal Permeabilitymentioning

confidence: 99%

Dynamic in vitro intestinal barrier model coupled to chip-based liquid chromatography mass spectrometry for oral bioavailability studies

et al. 2019

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In oral bioavailability studies, evaluation of the absorption and transport of drugs and food components across the intestinal barrier is crucial. Advances in the field of organ-on-a-chip technology have resulted in a dynamic gut-on-a-chip model that better mimics the in vivo microenvironment of the intestine. Despite a few recent integration attempts, ensuring a biologically relevant microenvironment while coupling with a fully online detection system still represents a major challenge. Herein, we designed an online technique to measure drug permeability and analyse unknown product formation across an intestinal epithelial layer of Caco-2 and HT29-MTX cells cultured on a flow-through Transwell system, while ensuring the quality and relevance of the biological model. Chip-based ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) was coupled to the dynamic Transwell system via a series of switching valves, thus allowing alternating measurements of the apical and basolateral sides of the in vitro model. Two trap columns were integrated for online sample pre-treatment and compatibility enhancement. Temporal analysis of the intestinal permeability was successfully demonstrated using verapamil as a model drug and ergotamine epimers as a model for natural toxins present in foods. Evidence was obtained that our newly developed dynamic system provided reliable results versus classical static in vitro models, and moreover, for the first time, epimer-specific transport is shown for ergotamine. Finally, initial experiments with the drug granisetron suggest that metabolic activity can be studied as well, thus highlighting the versatility of the bio-integrated online analysis system developed.

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Implementation of a dynamic intestinal gut-on-a-chip barrier model for transport studies of lipophilic dioxin congeners

Abstract: Novel microfluidic technologies allow the manufacture of in vitro organ-on-a-chip systems that hold great promise to adequately recapitulate the biophysical and functional complexity of organs found in vivo.

Cited by 39 publications

References 71 publications

Transcriptome comparisons of in vitro intestinal epithelia grown under static and microfluidic gut-on-chip conditions with in vivo human epithelia

Transcriptome comparisons of in vitro intestinal epithelia grown under static and microfluidic gut-on-chip conditions with in vivo human epithelia

Biomedical Application of Functional Materials in Organ-on-a-Chip

Dynamic in vitro intestinal barrier model coupled to chip-based liquid chromatography mass spectrometry for oral bioavailability studies

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