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      Microfluidic Organ-on-a-Chip Models of Human Intestine

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          Abstract

          Microfluidic organ-on-a-chip models of human intestine have been developed and used to study intestinal physiology and pathophysiology. In this article, we review this field and describe how microfluidic Intestine Chips offer new capabilities not possible with conventional culture systems or organoid cultures, including the ability to analyze contributions of individual cellular, chemical, and physical control parameters one-at-a-time; to coculture human intestinal cells with commensal microbiome for extended times; and to create human-relevant disease models. We also discuss potential future applications of human Intestine Chips, including how they might be used for drug development and personalized medicine.

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          Most cited references61

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          Organoids as an in vitro model of human development and disease.

          The in vitro organoid model is a major technological breakthrough that has already been established as an essential tool in many basic biology and clinical applications. This near-physiological 3D model facilitates an accurate study of a range of in vivo biological processes including tissue renewal, stem cell/niche functions and tissue responses to drugs, mutation or damage. In this Review, we discuss the current achievements, challenges and potential applications of this technique.
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            Shiga-toxin-producing Escherichia coli and haemolytic uraemic syndrome.

            Most cases of diarrhoea-associated haemolytic uraemic syndrome (HUS) are caused by Shiga-toxin-producing bacteria; the pathophysiology differs from that of thrombotic thrombocytopenic purpura. Among Shiga-toxin-producing Escherichia coli (STEC), O157:H7 has the strongest association worldwide with HUS. Many different vehicles, in addition to the commonly suspected ground (minced) beef, can transmit this pathogen to people. Antibiotics, antimotility agents, narcotics, and non-steroidal anti-inflammatory drugs should not be given to acutely infected patients, and we advise hospital admission and administration of intravenous fluids. Management of HUS remains supportive; there are no specific therapies to ameliorate the course. The vascular injury leading to HUS is likely to be well under way by the time infected patients seek medical attention for diarrhoea. The best way to prevent HUS is to prevent primary infection with Shiga-toxin-producing bacteria.
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              Advantages and challenges of microfluidic cell culture in polydimethylsiloxane devices.

              Culture of cells using various microfluidic devices is becoming more common within experimental cell biology. At the same time, a technological radiation of microfluidic cell culture device designs is currently in progress. Ultimately, the utility of microfluidic cell culture will be determined by its capacity to permit new insights into cellular function. Especially insights that would otherwise be difficult or impossible to obtain with macroscopic cell culture in traditional polystyrene dishes, flasks or well-plates. Many decades of heuristic optimization have gone into perfecting conventional cell culture devices and protocols. In comparison, even for the most commonly used microfluidic cell culture devices, such as those fabricated from polydimethylsiloxane (PDMS), collective understanding of the differences in cellular behavior between microfluidic and macroscopic culture is still developing. Moving in vitro culture from macroscopic culture to PDMS based devices can come with unforeseen challenges. Changes in device material, surface coating, cell number per unit surface area or per unit media volume may all affect the outcome of otherwise standard protocols. In this review, we outline some of the advantages and challenges that may accompany a transition from macroscopic to microfluidic cell culture. We focus on decisive factors that distinguish macroscopic from microfluidic cell culture to encourage a reconsideration of how macroscopic cell culture principles might apply to microfluidic cell culture.
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                Author and article information

                Contributors
                Journal
                Cell Mol Gastroenterol Hepatol
                Cell Mol Gastroenterol Hepatol
                Cellular and Molecular Gastroenterology and Hepatology
                Elsevier
                2352-345X
                2018
                24 April 2018
                : 5
                : 4
                : 659-668
                Affiliations
                [1 ]Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, Massachusetts
                [2 ]Department of Biomedical Engineering, The University of Texas at Austin, Austin, Texas
                [3 ]Department of Bioengineering and iBB - Institute for Bioengineering and Biosciences, Instituto Superior Técnico, University of Lisbon, Lisbon, Portugal
                [4 ]Graduate Program, Faculty of Biology, University of Freiburg, Freiburg, Germany
                [5 ]Graduate Program, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland
                [6 ]Vascular Biology Program and Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts
                [7 ]Harvard John A. Paulson School of Engineering and Applied Sciences, Cambridge, Massachusetts
                Author notes
                [] Correspondence Address correspondence to: Donald E. Ingber, MD, PhD, Wyss Institute at Harvard University, CLSB Building, 5 th floor, 3 Blackfan Circle, Boston, Massachusetts 02115. fax: 617-432-7048 don.ingber@ 123456wyss.harvard.edu
                [∗∗ ]Hyun Jung Kim, PhD, Department of Biomedical Engineering, The University of Texas at Austin, 107 West Dean Keeton Street, BME 4.202C, Austin, Texas 78712. hyunjung.kim@ 123456utexas.edu
                [a]

                Authors contributed equally.

                Article
                S2352-345X(17)30189-3
                10.1016/j.jcmgh.2017.12.010
                5924739
                29713674
                bcec0df5-8f1a-495a-acc4-ad858823e456
                © 2018 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 26 September 2017
                : 26 December 2017
                Categories
                Review

                organs-on-chips,gut-on-a-chip,intestine-on-a-chip,microfluidic,ecm, extracellular matrix,ibd, inflammatory bowel disease,pd, pharmacodynamics,pdms, polydimethylsiloxane,pk, pharmacokinetics,3d, 3-dimensional

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