A human gut-on-a-chip microdevice was used to coculture multiple commensal microbes in contact with living human intestinal epithelial cells for more than a week in vitro and to analyze how gut microbiome, inflammatory cells, and peristalsis-associated mechanical deformations independently contribute to intestinal bacterial overgrowth and inflammation. This in vitro model replicated results from past animal and human studies, including demonstration that probiotic and antibiotic therapies can suppress villus injury induced by pathogenic bacteria. By ceasing peristalsis-like motions while maintaining luminal flow, lack of epithelial deformation was shown to trigger bacterial overgrowth similar to that observed in patients with ileus and inflammatory bowel disease. Analysis of intestinal inflammation on-chip revealed that immune cells and lipopolysaccharide endotoxin together stimulate epithelial cells to produce four proinflammatory cytokines (IL-8, IL-6, IL-1, and TNF-) that are necessary and sufficient to induce villus injury and compromise intestinal barrier function. Thus, this human gut-on-a-chip can be used to analyze contributions of microbiome to intestinal pathophysiology and dissect disease mechanisms in a controlled manner that is not possible using existing in vitro systems or animal models.
Contributions of microbiome and mechanical deformation to intestinal bacterial overgrowth and inflammation in a human gut-on-a-chip.
Cell line
View SamplesStimulation of HL60 progenitor cells with either DMSO (1.25% v/v) or atRA (10E-07M) resulted in their differentiation into neutrophils within six days. Gene expression profiles across 12 600 genes were measured for the differentiation processes induced by DMSO and atRA at 0, 2, 4, 8, 12, and 18 h and daily thereafter until day 7 using oligonucleotide DNA microarrays.
Cell fates as high-dimensional attractor states of a complex gene regulatory network.
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View SamplesSilencing HoxA1 in vivo by intraductal delivery of nanoparticle-formulated siRNA reduced mammary tumor incidence by 75% , reduced cell proliferation, and prevented loss of ER and PR expression.
Silencing HoxA1 by intraductal injection of siRNA lipidoid nanoparticles prevents mammary tumor progression in mice.
Age, Specimen part
View SamplesSmoking represents a major risk factor for chronic obstructive pulmonary disease (COPD), but it is difficult to characterize smoke-induced injury responses under physiological breathing conditions in humans. Here we generated small airway-on-a-chip microdevices lined by living human bronchiolar epithelium from normal or COPD patients and connected them to an instrument that 'breathes' whole cigarette smoke in and out of the chips to study smoke-induced pathophysiology in vitro. We used microarrays to detail the global program of gene expression in well-differentiated epithelial cells following smoke exposure to recapitulate clinical pathologies and identify disease-specific responses.
Matched-Comparative Modeling of Normal and Diseased Human Airway Responses Using a Microengineered Breathing Lung Chip.
Specimen part, Disease, Treatment
View SamplesHere we describe a method for fabricating a primary human Small Intestine-on-a-Chip (Intestine Chip) containing epithelial cells isolated from healthy regions of intestinal biopsies. The primary epithelial cells are expanded as 3D organoids, dissociated, and cultured on a porous membrane within a microfluidic device with human intestinal microvascular endothelium cultured in a parallel microchannel under flow and cyclic deformation. In the Intestine Chip, the epithelium forms villi-like projections lined by polarized epithelial cells that undergo multi-lineage differentiation similar to that of intestinal organoids, however, these cells expose their apical surfaces to an open lumen and interface with endothelium. Transcriptomic analysis also indicates that the Intestine Chip more closely mimics whole human duodenum in vivo when compared to the duodenal organoids used to create the chips. Because fluids flowing through the lumen of the Intestine Chip can be collected continuously, sequential analysis of fluid samples can be used to quantify nutrient digestion, mucus secretion and establishment of intestinal barrier function over a period of multiple days in vitro. The Intestine Chip therefore may be useful as a research tool for applications where normal intestinal function is crucial, including studies of metabolism, nutrition, infection, and drug pharmacokinetics, as well as personalized medicine.
Development of a primary human Small Intestine-on-a-Chip using biopsy-derived organoids.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Effect of developmental NMDAR antagonism with CGP 39551 on aspartame-induced hypothalamic and adrenal gene expression.
Sex, Age, Specimen part
View SamplesGender dimorphism exists in the physiological response to diet and other environmental factors. Trans-hydrogenated fatty acid (TFA) intake is associated with an increase in coronary heart disease (CHD), and gender differences in the incidence of CHD are well documented. Neonatal administration of Monosodium Glutamate (MSG) causes stunted heart growth and hypoplasticity; and gender dimorphism at the growth hormone axis has been demonstrated in MSG-treated rodents. The identification of gender dimorphism in cardiac nutrigenomics may provide the basis for gender-specific medicine in the future.
Sex-dimorphism in cardiac nutrigenomics: effect of trans fat and/or monosodium glutamate consumption.
Sex, Specimen part
View SamplesChronic dietary aspartame may impair rodent insulin tolerance and may affect behavior. Previous studies have shown the aspartame effects may be modulated by developmental NMDA receptor antagonism. Present study was designed to assess effects of aspartame and NMDAR antagonism on components of the HPA axis.
Effect of developmental NMDAR antagonism with CGP 39551 on aspartame-induced hypothalamic and adrenal gene expression.
Sex, Age, Specimen part
View SamplesChronic dietary aspartame may impair rodent insulin tolerance and may affect behavior. Previous studies have shown the aspartame effects may be modulated by developmental NMDA receptor antagonism. Present study was designed to assess effects of aspartame and NMDAR antagonism on components of the HPA axis.
Effect of developmental NMDAR antagonism with CGP 39551 on aspartame-induced hypothalamic and adrenal gene expression.
Sex, Age, Specimen part
View SamplesThe primary aim of this project was to identify novel factors, in particular the cell-surface protein CD109, which regulate osteoclastogenesis. Microarray analysis was performed comparing two pre-osteoclast cell lines generated from the RAW 264.7 osteoclast cell line: one that has the capacity to fuse forming large multinucleated cells and one that does not fuse. It was found that CD109 was up-regulated by > 17-fold in the osteoclast forming cell line when compared to the cell line that does not fuse.
CD109 plays a role in osteoclastogenesis.
Specimen part, Cell line
View Samples