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https://www.readbyqxmd.com/read/29881844/a-pumpless-body-on-a-chip-model-using-a-primary-culture-of-human-intestinal-cells-and-a-3d-culture-of-liver-cells
#1
Huanhuan Joyce Chen, Paula Miller, Michael L Shuler
We describe an expanded modular gastrointestinal (GI) tract-liver system by co-culture of primary human intestinal epithelial cells (hIECs) and 3D liver mimic. The two organ body-on-chip design consisted of GI and liver tissue compartments that were connected by fluidic medium flow driven via gravity. The hIECs and HepG2 C3A liver cells in the co-culture system maintained high viability for at least 14 days in which hIECs differentiated into major cell types found in native human intestinal epithelium and the HepG2 C3A cells cultured on 3D polymer scaffold formed a liver micro-lobe like structure...
June 8, 2018: Lab on a Chip
https://www.readbyqxmd.com/read/29713662/move-over-caco-2-cells-human-induced-organoids-meet-gut-on-a-chip
#2
EDITORIAL
Camilla A Richmond, David T Breault
No abstract text is available yet for this article.
2018: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29693447/chronic-kidney-disease-uremic-milieu-and-its-effects-on-gut-bacterial-microbiota-dysbiosis
#3
Lee D Chaves, Daniel I McSkimming, Mark A Bryniarski, Amanda M Honan, Sham Abyad, Shruthi A Thomas, Steven Wells, Michael J Buck, Yijun Sun, Robert J Genco, Richard J Quigg, Rabi Yacoub
Several lines of evidence suggest that gut bacterial microbiota is altered in patients with chronic kidney disease (CKD), though the mechanism of which this dysbiosis takes place is not well understood. Recent studies delineated changes in gut microbiota in both CKD patients and experimental animal models using microarray chips. We present 16S ribosomal RNA gene sequencing of both stool pellets and small bowel contents of C57Bl/6J mice that underwent a remnant kidney model, and establish that changes in microbiota take place in the early gastrointestinal track...
April 25, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29445080/modeling-radiation-injury-induced-cell-death-and-countermeasure-drug-responses-in-a-human-gut-on-a-chip
#4
Sasan Jalili-Firoozinezhad, Rachelle Prantil-Baun, Amanda Jiang, Ratnakar Potla, Tadanori Mammoto, James C Weaver, Thomas C Ferrante, Hyun Jung Kim, Joaquim M S Cabral, Oren Levy, Donald E Ingber
Studies on human intestinal injury induced by acute exposure to γ-radiation commonly rely on use of animal models because culture systems do not faithfully mimic human intestinal physiology. Here we used a human Gut-on-a-Chip (Gut Chip) microfluidic device lined by human intestinal epithelial cells and vascular endothelial cells to model radiation injury and assess the efficacy of radiation countermeasure drugs in vitro. Exposure of the Gut Chip to γ-radiation resulted in increased generation of reactive oxygen species, cytotoxicity, apoptosis, and DNA fragmentation, as well as villus blunting, disruption of tight junctions, and compromise of intestinal barrier integrity...
February 14, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29398302/organs-on-a-chip-current-applications-and-consideration-points-for-in-vitro-adme-tox-studies
#5
REVIEW
Seiichi Ishida
Assay systems using in vitro cultured cells are increasingly applied for evaluation of the efficacy, safety, and toxicity of drug candidates. In vitro cell-based assays have two main applications in the drug discovery process: searching for a compound that is effective against the target disease (seed investigation) and confirmation of safety during use of the identified compounds (safety assessment). Currently available in vitro cell-based assays have been designed to evaluate the efficacy and toxicity in single organs, but the in vivo pharmacokinetics and pharmacodynamics of the administered drug candidates have not been considered...
February 2018: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/29186668/emulation-of-colonic-oxygen-gradients-in-a-microdevice
#6
David I Walsh, E Victoria Dydek, Jaclyn Y Lock, Taylor L Carlson, Rebecca L Carrier, David S Kong, Catherine R Cabrera, Todd Thorsen
Gut-on-a-chip in vitro modeling is an emerging field, as the human gut epithelium and gut microbiome have been recently identified as novel drug targets for a wide variety of diseases. Realistic in vitro gut models require a variety of precise environmental cues, such as chemical and gas gradients, in combination with substrates like mucus that support the growth of microbial communities. This technical brief describes a microfluidic architecture capable of developing a physiologically relevant oxygen gradient that emulates the oxygen profile proximal to the epithelial inner lining of the human colon...
April 2018: SLAS Technology
https://www.readbyqxmd.com/read/29175062/organ-body-on-a-chip-based-on-microfluidic-technology-for-drug-discovery
#7
REVIEW
Hiroshi Kimura, Yasuyuki Sakai, Teruo Fujii
Although animal experiments are indispensable for preclinical screening in the drug discovery process, various issues such as ethical considerations and species differences remain. To solve these issues, cell-based assays using human-derived cells have been actively pursued. However, it remains difficult to accurately predict drug efficacy, toxicity, and organs interactions, because cultivated cells often do not retain their original organ functions and morphologies in conventional in vitro cell culture systems...
February 2018: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/29116458/3d-gut-liver-chip-with-a-pk-model-for-prediction-of-first-pass-metabolism
#8
Dong Wook Lee, Sang Keun Ha, Inwook Choi, Jong Hwan Sung
Accurate prediction of first-pass metabolism is essential for improving the time and cost efficiency of drug development process. Here, we have developed a microfluidic gut-liver co-culture chip that aims to reproduce the first-pass metabolism of oral drugs. This chip consists of two separate layers for gut (Caco-2) and liver (HepG2) cell lines, where cells can be co-cultured in both 2D and 3D forms. Both cell lines were maintained well in the chip, verified by confocal microscopy and measurement of hepatic enzyme activity...
November 7, 2017: Biomedical Microdevices
https://www.readbyqxmd.com/read/28811479/membrane-free-culture-and-real-time-barrier-integrity-assessment-of-perfused-intestinal-epithelium-tubes
#9
Sebastiaan J Trietsch, Elena Naumovska, Dorota Kurek, Meily C Setyawati, Marianne K Vormann, Karlijn J Wilschut, Henriëtte L Lanz, Arnaud Nicolas, Chee Ping Ng, Jos Joore, Stefan Kustermann, Adrian Roth, Thomas Hankemeier, Annie Moisan, Paul Vulto
In vitro models that better reflect in vivo epithelial barrier (patho-)physiology are urgently required to predict adverse drug effects. Here we introduce extracellular matrix-supported intestinal tubules in perfused microfluidic devices, exhibiting tissue polarization and transporter expression. Forty leak-tight tubules are cultured in parallel on a single plate and their response to pharmacological stimuli is recorded over 125 h using automated imaging techniques. A study comprising 357 gut tubes is performed, of which 93% are leak tight before exposure...
August 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28752430/integrated-gut-and-liver-microphysiological-systems-for-quantitative-in-vitro-pharmacokinetic-studies
#10
Nikolaos Tsamandouras, Wen Li Kelly Chen, Collin D Edington, Cynthia L Stokes, Linda G Griffith, Murat Cirit
Investigation of the pharmacokinetics (PK) of a compound is of significant importance during the early stages of drug development, and therefore several in vitro systems are routinely employed for this purpose. However, the need for more physiologically realistic in vitro models has recently fueled the emerging field of tissue-engineered 3D cultures, also referred to as organs-on-chips, or microphysiological systems (MPSs). We have developed a novel fluidic platform that interconnects multiple MPSs, allowing PK studies in multi-organ in vitro systems along with the collection of high-content quantitative data...
September 2017: AAPS Journal
https://www.readbyqxmd.com/read/28730936/an-industry-update-what-is-the-latest-news-in-therapeutic-delivery
#11
Iain Simpson
This Industry Update covers the period from 1 through 30 April 2017, and is based on information sourced from company press releases, scientific literature, patents and various news websites. Biogen expanded its portfolio of developmental drugs targeting neurological diseases by licensing a drug from Bristol-Myers Squibb which is currently under investigation for the treatment of progressive supranuclear palsy. Takeda announced a deal with NuBiyota focused on developing treatments for gastrointestinal disorders, based on the manipulation of microbes living in the gut...
July 2017: Therapeutic Delivery
https://www.readbyqxmd.com/read/28598479/organs-on-chips-with-integrated-electrodes-for-trans-epithelial-electrical-resistance-teer-measurements-of-human-epithelial-barrier-function
#12
Olivier Y F Henry, Remi Villenave, Michael J Cronce, William D Leineweber, Maximilian A Benz, Donald E Ingber
Trans-epithelial electrical resistance (TEER) is broadly used as an experimental readout and a quality control assay for measuring the integrity of epithelial monolayers cultured under static conditions in vitro, however, there is no standard methodology for its application to microfluidic organ-on-a-chip (organ chip) cultures. Here, we describe a new microfluidic organ chip design that contains embedded electrodes, and we demonstrate its utility for assessing formation and disruption of barrier function both within a human lung airway chip lined by a fully differentiated mucociliary human airway epithelium and in a human gut chip lined by intestinal epithelial cells...
June 27, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/28488235/emulating-host-microbiome-ecosystem-of-human-gastrointestinal-tract-in-vitro
#13
REVIEW
Gun-Seok Park, Min Hee Park, Woojung Shin, Connie Zhao, Sameer Sheikh, So Jung Oh, Hyun Jung Kim
The human gut microbiome performs prodigious physiological functions such as production of microbial metabolites, modulation of nutrient digestion and drug metabolism, control of immune system, and prevention of infection. Paradoxically, gut microbiome can also negatively orchestrate the host responses in diseases or chronic disorders, suggesting that the regulated and balanced host-gut microbiome crosstalk is a salient prerequisite in gastrointestinal physiology. To understand the pathophysiological role of host-microbiome crosstalk, it is critical to recreate in vivo relevant models of the host-gut microbiome ecosystem in human...
June 2017: Stem Cell Reviews
https://www.readbyqxmd.com/read/28468904/host-genome-influence-on-gut-microbial-composition-and-microbial-prediction-of-complex-traits-in-pigs
#14
Amelia Camarinha-Silva, Maria Maushammer, Robin Wellmann, Marius Vital, Siegfried Preuss, Jörn Bennewitz
The aim of the present study was to analyze the interplay between gastrointestinal tract (GIT) microbiota, host genetics, and complex traits in pigs using extended quantitative-genetic methods. The study design consisted of 207 pigs that were housed and slaughtered under standardized conditions, and phenotyped for daily gain, feed intake, and feed conversion rate. The pigs were genotyped with a standard 60 K SNP chip. The GIT microbiota composition was analyzed by 16S rRNA gene amplicon sequencing technology...
July 2017: Genetics
https://www.readbyqxmd.com/read/28451924/microfluidic-gut-on-a-chip-with-three-dimensional-villi-structure
#15
Kyu-Young Shim, Dongwook Lee, Jeonghun Han, Nam-Trung Nguyen, Sungsu Park, Jong Hwan Sung
Current in vitro gut models lack physiological relevance, and various approaches have been taken to improve current cell culture models. For example, mimicking the three-dimensional (3D) tissue structure or fluidic environment has been shown to improve the physiological function of gut cells. Here, we incorporated a collagen scaffold that mimics the human intestinal villi into a microfluidic device, thus providing cells with both 3D tissue structure and fluidic shear. We hypothesized that the combined effect of 3D structure and fluidic shear may provide cells with adequate stimulus to induce further differentiation and improve physiological relevance...
June 2017: Biomedical Microdevices
https://www.readbyqxmd.com/read/28146569/human-gut-on-a-chip-supports-polarized-infection-of-coxsackie-b1-virus-in-vitro
#16
Remi Villenave, Samantha Q Wales, Tiama Hamkins-Indik, Efstathia Papafragkou, James C Weaver, Thomas C Ferrante, Anthony Bahinski, Christopher A Elkins, Michael Kulka, Donald E Ingber
Analysis of enterovirus infection is difficult in animals because they express different virus receptors than humans, and static cell culture systems do not reproduce the physical complexity of the human intestinal epithelium. Here, using coxsackievirus B1 (CVB1) as a prototype enterovirus strain, we demonstrate that human enterovirus infection, replication and infectious virus production can be analyzed in vitro in a human Gut-on-a-Chip microfluidic device that supports culture of highly differentiated human villus intestinal epithelium under conditions of fluid flow and peristalsis-like motions...
2017: PloS One
https://www.readbyqxmd.com/read/28113162/omics-tech-gut-on-a-chip-and-bacterial-engineering-new-approaches-for-treating-inflammatory-bowel-diseases
#17
Leslie Mertz
It was six years ago that fecal transplantation first received prominent media attention and the public began to fully appreciate that the bacteria and other microbes in their bodies could have a real impact on health.
September 2016: IEEE Pulse
https://www.readbyqxmd.com/read/28074384/microfluidic-gut-liver-chip-for-reproducing-the-first-pass-metabolism
#18
Aerim Choe, Sang Keun Ha, Inwook Choi, Nakwon Choi, Jong Hwan Sung
After oral intake of drugs, drugs go through the first pass metabolism in the gut and the liver, which greatly affects the final outcome of the drugs' efficacy and side effects. The first pass metabolism is a complex process involving the gut and the liver tissue, with transport and reaction occurring simultaneously at various locations, which makes it difficult to be reproduced in vitro with conventional cell culture systems. In an effort to tackle this challenge, here we have developed a microfluidic gut-liver chip that can reproduce the dynamics of the first pass metabolism...
March 2017: Biomedical Microdevices
https://www.readbyqxmd.com/read/28062270/the-role-of-gut-microbiota-in-health-and-disease-in%C3%A2-vitro-modeling-of-host-microbe-interactions-at-the-aerobe-anaerobe-interphase-of-the-human-gut
#19
REVIEW
Julius Z H von Martels, Mehdi Sadaghian Sadabad, Arno R Bourgonje, Tjasso Blokzijl, Gerard Dijkstra, Klaas Nico Faber, Hermie J M Harmsen
The microbiota of the gut has many crucial functions in human health. Dysbiosis of the microbiota has been correlated to a large and still increasing number of diseases. Recent studies have mostly focused on analyzing the associations between disease and an aberrant microbiota composition. Functional studies using (in vitro) gut models are required to investigate the precise interactions that occur between specific bacteria (or bacterial mixtures) and gut epithelial cells. As most gut bacteria are obligate or facultative anaerobes, studying their effect on oxygen-requiring human gut epithelial cells is technically challenging...
April 2017: Anaerobe
https://www.readbyqxmd.com/read/27743363/analysis-of-milk-oligosaccharides-by-mass-spectrometry
#20
Lauren D Wu, L Renee Ruhaak, Carlito B Lebrilla
Human milk oligosaccharides (HMOs) are a highly abundant constituent in human milk, and its protective and prebiotic properties have attracted considerable attention. HMOs have been shown to directly and indirectly benefit the overall health of the infant due to a number of functions including serving as a beneficial food for gut bacteria, block to pathogens, and aiding in brain development. Researchers are currently exploring whether these structures may act as possible disease and nutrition biomarkers. Because of this, rapid-throughput methods are desired to investigate biological activity in large patient sets...
2017: Methods in Molecular Biology
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