A5070159648- 3D Printing in Biomedical Research
- Cancer Cells and Metastasis
- Gut microbiota and health
- Probiotics and Fermented Foods
- Escherichia coli research studies
- Pluripotent Stem Cells Research
- Digestive system and related health
- Clostridium difficile and Clostridium perfringens research
- Helicobacter pylori-related gastroenterology studies
- Barrier Structure and Function Studies
- Pharmacogenetics and Drug Metabolism
- Planarian Biology and Electrostimulation
- Drug Transport and Resistance Mechanisms
- Renal and related cancers
- Viral gastroenteritis research and epidemiology
- Gastrointestinal motility and disorders
- Bacterial Infections and Vaccines
- Single-cell and spatial transcriptomics
- Bacterial Genetics and Biotechnology
- Cancer Immunotherapy and Biomarkers
- COVID-19 Clinical Research Studies
- Pancreatitis Pathology and Treatment
- Microbial Inactivation Methods
- Microfluidic and Bio-sensing Technologies
- Cellular transport and secretion
Cincinnati Children's Hospital Medical Center
2020-2024
Emulate (United States)
2019-2021
Inspire
2019
Harvard University Press
2019
Harvard University
2018-2019
Boston Children's Hospital
2015
Novartis (Switzerland)
2015
Novartis (Italy)
2013-2014
Toscana Life Sciences
2013
Abstract Here we describe a method for fabricating primary human Small Intestine-on-a-Chip (Intestine Chip) containing epithelial cells isolated from healthy regions of intestinal biopsies. The are expanded as 3D organoids, dissociated, and cultured on porous membrane within microfluidic device with microvascular endothelium in parallel microchannel under flow cyclic deformation. In the Intestine Chip, epithelium forms villi-like projections lined by polarized that undergo multi-lineage...
Background & AimsThe mucus layer in the human colon protects against commensal bacteria and pathogens, defects its unique bilayered structure contribute to intestinal disorders, such as ulcerative colitis. However, our understanding of physiology is limited by lack vitro models that replicate colonic function. Here, we investigated if combining organ-on-a-chip organoid technologies can be leveraged develop a human-relevant model physiology.MethodsA colon-on-a-chip (Colon Chip) microfluidic...
Induction of intestinal drug metabolizing enzymes can complicate the development new drugs, owing to potential cause drug-drug interactions (DDIs) leading changes in pharmacokinetics, safety and efficacy. The a human-relevant model adult intestine that accurately predicts CYP450 induction could help address this challenge as species differences preclude extrapolation from animals. Here, we combined organoids Organs-on-Chips technology create human Duodenum Intestine-Chip emulates tissue...
Species-specific differences in tolerance to infection are exemplified by the high susceptibility of humans enterohemorrhagic Escherichia coli (EHEC) infection, whereas mice relatively resistant this pathogen. This intrinsic species-specific difference EHEC limits translation murine research human. Furthermore, studying mechanisms underlying differential is a difficult problem due complex vivo interactions between host, pathogen, and disparate commensal microbial communities. We utilize...
Abstract Understanding the complexities of human brain’s function in health and disease is a formidable challenge neuroscience. While traditional models like animals offer valuable insights, they often fall short accurately mirroring biology drug responses. Moreover, recent legislation has underscored need for more predictive that represent physiology. To address this requirement, human-derived cell cultures have emerged as crucial alternative biomedical research. However, static culture...
The limited availability of organoid systems that mimic the molecular signatures and architecture human intestinal epithelium has been an impediment to allowing them be harnessed for development therapeutics as well physiological insights. We developed a microphysiological Organ-on-Chip (Emulate, Inc, Boston, MA) platform designed properties leading insights into barrier integrity.We combined biopsy-derived leucine-rich repeat-containing G-protein-coupled receptor 5-positive organoids...
SslE is a zinc-metalloprotease involved in the degradation of mucin substrates and recently proposed as potential vaccine candidate against pathogenic E. coli. In this paper, by exploiting human vitro model mucus-secreting cells, we demonstrated that bacteria expressing have metabolic benefit which results an increased growth rate postulating importance antigen enhancing coli fitness. We also observed expression facilitates penetration mucus favouring adhesion to host cells. Moreover, found...
Clostridium difficile is a cause of antibiotic-associated diarrhea and colitis, healthcare-associated intestinal disease. Colonization the gut critical step in course infection. The C. lipoprotein CD0873 was identified as putative adhesin through bioinformatics approach. Surface exposure confirmed mutant generated. showed significant reduction adherence to Caco-2 cells wild-type bacteria preincubated with anti-CD0873 antibodies significantly decreased cells. In addition, we demonstrated that...
Modeling host-pathogen interactions with human intestinal epithelia using enteroid monolayers on permeable supports (such as Transwells) represents an alternative to animal studies or use of colon cancer-derived cell lines. However, the static monolayer model does not expose epithelial cells mechanical forces normally present in intestine, including luminal flow and serosal blood (shear force) peristaltic forces.
This study showed that polarized enteroid models in which there is no basolateral Wnt3a, are differentiated, regardless of the Wnt3a status apical media. The supports concept human intestine villus differentiation not an all or none phenomenon, demonstrating at different days after lack Wnt exposure, clusters genes and proteins exist geographically along with domains having functions.
The contribution of Clostridium difficile toxin A and B (TcdA TcdB) to cellular intoxication has been studied extensively, but their impact on bacterial colonization remains unclear. By setting up 2- 3-dimensional in vitro models polarized gut epithelium, we investigated how C. infection is affected by host cell polarity whether TcdA TcdB contribute such events. Indeed, observed that adhesion penetration the mucosal barrier are substantially enhanced poorly or ethylene glycol tetraacetic...
Translocation of the nasopharyngeal barrier by Neisseria meningitidis occurs via an intracellular microtubule-dependent pathway and represents a crucial step in its pathogenesis. Despite this fact, interaction invasive meningococci with host subcellular compartments resulting impact on their organization function have not been investigated. The influence serogroup B strain MC58 cell polarity trafficking system was assessed confocal microscopy visualization different plasma...
The intestinal mucosa is a complex physical and biochemical barrier that fulfills myriad of important functions. It enables the transport, absorption, metabolism nutrients xenobiotics while facilitating symbiotic relationship with microbiota restricting invasion microorganisms. Functional interaction between various cell types their environment vital to establish maintain tissue homeostasis. Modeling these interactions integrated physiology in vitro formidable goal potential transform way...
Abstract Induction of intestinal drug metabolizing enzymes can complicate the development new drugs, owing to potential cause drug-drug interactions (DDIs) leading changes in pharmacokinetics, safety and efficacy. The a human relevant model adult intestine that accurately predicts CYP450 induction could help address this challenge as species differences preclude extrapolation from animals. Here, we combined organoids Organ-Chip technology create Duodenum Intestine-Chip emulates tissue...
Nearly all human organs are lined with epithelial tissues, comprising one or multiple layers of tightly connected cells organized into three-dimensional (3D) structures. One the main functions epithelia is formation barriers that protect underlining tissues against physical and chemical insults infectious agents. In addition, mediate transport nutrients, hormones, other signaling molecules, often creating biochemical gradients guide cell positioning compartmentalization within organ. Owing...
The intestinal mucosa is a complex physical and biochemical barrier that fulfills myriad of important functions. It enables the transport, absorption, metabolism nutrients xenobiotics while facilitating symbiotic relationship with microbiota restricting invasion microorganisms. Functional interaction between various cell types their environment vital to establish maintain tissue homeostasis. Modeling these interactions integrated physiology in vitro formidable goal potential transform way...
ABSTRACT Background Species-specific differences in tolerance to infection are exemplified by the high susceptibility of humans enterohemorrhagic E. coli (EHEC) whereas mice relatively resistant this pathogen. This intrinsic species-specific difference EHEC limits translation murine research human. Furthermore, studying mechanisms underlying differential is a difficult problem due complex vivo interactions between host, pathogen, and disparate commensal microbial communities. Results We...
ABSTRACT Background & Aims The mucus layer in the human colon protects against commensal bacteria and pathogens, defects its unique bilayered structure contribute to intestinal disorders, such as ulcerative colitis. However, our understanding of physiology is limited by lack vitro models that replicate colonic function. Here, we investigated if combining organ-on-a-chip organoid technologies can be leveraged develop a human-relevant model physiology. Methods A colon-on-a-chip (Colon...
ABSTRACT Modeling host-pathogen interactions with human intestinal epithelia using enteroid monolayers on permeable supports (such as Transwells) represents an alternative to animal studies or use of colon cancer-derived cell lines. However, the static monolayer model does not expose epithelial cells mechanical forces normally present in intestine, including luminal flow and serosal blood (shear force) peristaltic forces. To determine contribution functional response small intestine a...