Microfluidic chip for culturing intestinal epithelial cell layers: Characterization and comparison of drug transport between dynamic and static models

Kulthong, Kornphimol; Duivenvoorde, Loes P. M.; Sun, Huaifeng; Confederat, Samuel; Wu, Jianjun; Spenkelink, Bert; Haan, Laura de; Marin, Victor Augustus; Zande, Meike van der; Bouwmeester, Hans

doi:10.1016/j.tiv.2020.104815

Cited by 47 publications

(30 citation statements)

References 64 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: 83%

“…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: 83%

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

Self Cite

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“…Following culture in this manner for 21 days, caco-2 cells form a continuous epithelium with greater height than equivalent transwell cultures that have an enhanced barrier function. Caco-2 cell differentiation was comparable with static cultures in this model (Kulthong et al, 2020).…”

Section: Intestine Modelsmentioning

confidence: 53%

“…In Micronit's gut-on-chip model, Caco-2 cells are subjected to flow at 100 µL/h producing a shear stress of ∼0.02-0.17 mPa at the cell surface (Kulthong et al, 2020). Following culture in this manner for 21 days, caco-2 cells form a continuous epithelium with greater height than equivalent transwell cultures that have an enhanced barrier function.…”

Section: Intestine Modelsmentioning

confidence: 99%

Mechanical Stimulation: A Crucial Element of Organ-on-Chip Models

Thompson

Knight

et al. 2020

Front. Bioeng. Biotechnol.

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Organ-on-chip (OOC) systems recapitulate key biological processes and responses in vitro exhibited by cells, tissues, and organs in vivo. Accordingly, these models of both health and disease hold great promise for improving fundamental research, drug development, personalized medicine, and testing of pharmaceuticals, food substances, pollutants etc. Cells within the body are exposed to biomechanical stimuli, the nature of which is tissue specific and may change with disease or injury. These biomechanical stimuli regulate cell behavior and can amplify, annul, or even reverse the response to a given biochemical cue or drug candidate. As such, the application of an appropriate physiological or pathological biomechanical environment is essential for the successful recapitulation of in vivo behavior in OOC models. Here we review the current range of commercially available OOC platforms which incorporate active biomechanical stimulation. We highlight recent findings demonstrating the importance of including mechanical stimuli in models used for drug development and outline emerging factors which regulate the cellular response to the biomechanical environment. We explore the incorporation of mechanical stimuli in different organ models and identify areas where further research and development is required. Challenges associated with the integration of mechanics alongside other OOC requirements including scaling to increase throughput and diagnostic imaging are discussed. In summary, compelling evidence demonstrates that the incorporation of biomechanical stimuli in these OOC or microphysiological systems is key to fully replicating in vivo physiology in health and disease.

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Patient‐Specific Organoid and Organ‐on‐a‐Chip: 3D Cell‐Culture Meets 3D Printing and Numerical Simulation

et al. 2021

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The last few decades have witnessed diversified in vitro models to recapitulate the architecture and function of living organs or tissues and contribute immensely to advances in life science. Two novel 3D cell culture models: 1) Organoid, promoted mainly by the developments of stem cell biology and 2) Organ‐on‐a‐chip, enhanced primarily due to microfluidic technology, have emerged as two promising approaches to advance the understanding of basic biological principles and clinical treatments. This review describes the comparable distinct differences between these two models and provides more insights into their complementarity and integration to recognize their merits and limitations for applicable fields. The convergence of the two approaches to produce multi‐organoid‐on‐a‐chip or human organoid‐on‐a‐chip is emerging as a new approach for building 3D models with higher physiological relevance. Furthermore, rapid advancements in 3D printing and numerical simulations, which facilitate the design, manufacture, and results‐translation of 3D cell culture models, can also serve as novel tools to promote the development and propagation of organoid and organ‐on‐a‐chip systems. Current technological challenges and limitations, as well as expert recommendations and future solutions to address the promising combinations by incorporating organoids, organ‐on‐a‐chip, 3D printing, and numerical simulation, are also summarized.

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Microfluidic chip for culturing intestinal epithelial cell layers: Characterization and comparison of drug transport between dynamic and static models

Cited by 47 publications

References 64 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

Mechanical Stimulation: A Crucial Element of Organ-on-Chip Models

Patient‐Specific Organoid and Organ‐on‐a‐Chip: 3D Cell‐Culture Meets 3D Printing and Numerical Simulation

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