scholarly journals Multi-Sensors Integration in a Human Gut-On-Chip Platform

Proceedings ◽  
2018 ◽  
Vol 2 (13) ◽  
pp. 1022
Author(s):  
Lucia Giampetruzzi ◽  
Amilcare Barca ◽  
Flavio Casino ◽  
Simonetta Capone ◽  
Tiziano Verri ◽  
...  
Keyword(s):  
Parameter Analysis ◽  
Disease Modelling ◽  
Human Intestine ◽  
Human Gut ◽  
Conventional Culture ◽  
Gut Epithelium ◽  
Human Disorders ◽  
On Chip ◽  
And Personalized Medicine

In the conventional culture systems in vitro, the challenging organoid approach have recently been overcome by the development of microfluidic Organ Chip models of human intestine. The potential future applications of Intestine-on-Chips in disease modelling, drug development and personalized medicine are leading research to identify and investigate limitations of modern chip-based systems and to focus the attention on the gut epithelium and its specific barrier function playing a significant role in many human disorders and diseases. In this paper, we propose and discuss the importance to implement a multi-parameter analysis on an engineered platform for developing an Epithelial Gut On Chip model.

scholarly journals Generation of defined neural populations from pluripotent stem cells

2018 ◽  
Vol 373 (1750) ◽  
pp. 20170214 ◽  
Author(s):  
Sarah F. McComish ◽  
Maeve A. Caldwell
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Embryonic Stem ◽  
Cell Types ◽  
Disease Modelling ◽  
Human Neural Stem Cells ◽  
Neural Populations ◽  
Human Disorders ◽  
Induced Pluripotent

Effective and efficient generation of human neural stem cells and subsequently functional neural populations from pluripotent stem cells has facilitated advancements in the study of human development and disease modelling. This review will discuss the established protocols for the generation of defined neural populations including regionalized neurons and astrocytes, oligodendrocytes and microglia. Early protocols were established in embryonic stem cells (ESC) but the discovery of induced pluripotent stem cells (iPSC) in 2006 provided a new platform for modelling human disorders of the central nervous system (CNS). The ability to produce patient- and disease-specific iPSC lines has created a new age of disease modelling. Human iPSC may be derived from adult somatic cells and subsequently patterned into numerous distinct cell types. The ability to derive defined and regionalized neural populations from iPSC provides a powerful in vitro model of CNS disorders. This article is part of the theme issue ‘Designer human tissue: coming to a lab near you’.

scholarly journals Complex human gut microbiome cultured in anaerobic human intestine chips

2018 ◽  
Author(s):  
Sasan Jalili-Firoozinezhad ◽  
Francesca S. Gazzaniga ◽  
Elizabeth L. Calamari ◽  
Diogo M. Camacho ◽  
Cicely W. Fadel ◽  
...  
Keyword(s):  
Microbial Communities ◽  
Intestinal Epithelium ◽  
Anaerobic Bacteria ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Human Intestine ◽  
Human Gut ◽  
Human Organ ◽  
Human Intestinal Epithelium

The diverse bacterial populations that comprise the commensal microbiota of the human intestine play a central role in health and disease, yet no method is available to sustain these complex microbial communities in direct contact with living human intestinal cells and their overlying mucus layer in vitro. Here we describe a human Organ-on-a-Chip (Organ Chip) microfluidic platform that permits control and real-time assessment of physiologically-relevant oxygen gradients, and which enables co-culture of living human intestinal epithelium with stable communities of aerobic and anaerobic human gut microbiota. When compared to aerobic co-culture conditions, establishment of a transluminal hypoxia gradient sustained higher microbial diversity with over 200 unique operational taxonomic units (OTUs) from 11 different genera, and an abundance of obligate anaerobic bacteria with ratios of Firmicutes and Bacteroidetes similar to those observed in human feces, in addition to increasing intestinal barrier function. The ability to culture human intestinal epithelium overlaid by complex human gut microbial communities within microfluidic Intestine Chips may enable investigations of host-microbiome interactions that were not possible previously, and serve as a discovery tool for development of new microbiome-related therapeutics, probiotics, and nutraceuticals.

scholarly journals Cell type-specific changes in transcriptomic profiles of endothelial cells, iPSC-derived neurons and astrocytes cultured on microfluidic chips

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
H. H. T. Middelkamp ◽  
A. H. A. Verboven ◽  
A. G. De Sá Vivas ◽  
C. Schoenmaker ◽  
T. M. Klein Gunnewiek ◽  
...  
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Cell Types ◽  
Future Application ◽  
Microfluidic Chips ◽  
Cell Type ◽  
Brain Physiology ◽  
Conventional Culture ◽  
On Chip

AbstractIn vitro neuronal models are essential for studying neurological physiology, disease mechanisms and potential treatments. Most in vitro models lack controlled vasculature, despite its necessity in brain physiology and disease. Organ-on-chip models offer microfluidic culture systems with dedicated micro-compartments for neurons and vascular cells. Such multi-cell type organs-on-chips can emulate neurovascular unit (NVU) physiology, however there is a lack of systematic data on how individual cell types are affected by culturing on microfluidic systems versus conventional culture plates. This information can provide perspective on initial findings of studies using organs-on-chip models, and further optimizes these models in terms of cellular maturity and neurovascular physiology. Here, we analysed the transcriptomic profiles of co-cultures of human induced pluripotent stem cell (hiPSC)-derived neurons and rat astrocytes, as well as one-day monocultures of human endothelial cells, cultured on microfluidic chips. For each cell type, large gene expression changes were observed when cultured on microfluidic chips compared to conventional culture plates. Endothelial cells showed decreased cell division, neurons and astrocytes exhibited increased cell adhesion, and neurons showed increased maturity when cultured on a microfluidic chip. Our results demonstrate that culturing NVU cell types on microfluidic chips changes their gene expression profiles, presumably due to distinct surface-to-volume ratios and substrate materials. These findings inform further NVU organ-on-chip model optimization and support their future application in disease studies and drug testing.

scholarly journals Modeling SARS-CoV-2 infection in vitro with a human intestine-on-chip device

2020 ◽  
Author(s):  
Yaqiong Guo ◽  
Ronghua Luo ◽  
Yaqing Wang ◽  
Pengwei Deng ◽  
Min Zhang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Viral Infection ◽  
Morphological Changes ◽  
Gastrointestinal Symptoms ◽  
Transcriptional Analysis ◽  
Infection Model ◽  
Human Intestine ◽  
Junction Protein ◽  
On Chip

ABSTRACTCoronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2) has given rise to a global pandemic. The gastrointestinal symptoms of some COVID-19 patients are underestimated. There is an urgent need to develop physiologically relevant model that can accurately reflect human response to viral infection. Here, we report the creation of a biomimetic human intestine infection model on a chip system that allows to recapitulate the intestinal injury and immune response induced by SARS-CoV-2, for the first time. The microengineered intestine-on-chip device contains human intestinal epithelium (co-cultured human intestinal epithelial Caco-2 cells and mucin secreting HT-29 cells) lined in upper channel and vascular endothelium (human umbilical vein endothelial cells, HUVECs) in a parallel lower channel under fluidic flow condition, sandwiched by a porous PDMS membrane coated with extracellular matrix (ECM). At day 3 post-infection of SARS-CoV-2, the intestine epithelium showed high susceptibility to viral infection and obvious morphological changes with destruction of intestinal villus, dispersed distribution of mucus secreting cells and reduced expression of tight junction (E-cadherin), indicating the destruction of mucous layer and the integrity of intestinal barrier caused by virus. Moreover, the endothelium exhibited abnormal cell morphology with disrupted expression of adherent junction protein (VE-cadherin). Transcriptional analysis revealed the abnormal RNA and protein metabolism, as well as activated immune responses in both epithelial and endothelial cells after viral infection (e.g., up-regulated cytokine genes, TNF signaling and NF-kappa B signaling-related genes). This bioengineered in vitro model system can mirror the human relevant pathophysiology and response to viral infection at the organ level, which is not possible in existing in vitro culture systems. It may provide a promising tool to accelerate our understanding of COVID-19 and devising novel therapies.

scholarly journals Gut-on-chip: Recreating human intestine in vitro

2020 ◽  
Vol 11 ◽  
pp. 204173142096531
Author(s):  
Yunqing Xiang ◽  
Hui Wen ◽  
Yue Yu ◽  
Mingqiang Li ◽  
Xiongfei Fu ◽  
...  
Keyword(s):  
Cell Biology ◽  
Intestinal Flora ◽  
In Vitro Models ◽  
Intestinal Microbiome ◽  
Human Gut ◽  
Intestinal Microbes ◽  
Number Of Microorganisms ◽  
On Chip

The human gut is important for food digestion and absorption, as well as a venue for a large number of microorganisms that coexist with the host. Although numerous in vitro models have been proposed to study intestinal pathology or interactions between intestinal microbes and host, they are far from recapitulating the real intestinal microenvironment in vivo. To assist researchers in further understanding gut physiology, the intestinal microbiome, and disease processes, a novel technology primarily based on microfluidics and cell biology, called “gut-on-chip,” was developed to simulate the structure, function, and microenvironment of the human gut. In this review, we first introduce various types of gut-on-chip systems, then highlight their applications in drug pharmacokinetics, host–gut microbiota crosstalk, and nutrition metabolism. Finally, we discuss challenges in this field and prospects for better understanding interactions between intestinal flora and human hosts, and then provide guidance for clinical treatment of related diseases.

In vitro study of the interaction between human gut microbiota and herbal extracts using willow bark extract as an example

Planta Medica ◽  
2016 ◽  
Vol 81 (S 01) ◽  
pp. S1-S381
Author(s):  
EM Pferschy-Wenzig ◽  
K Koskinen ◽  
C Moissl-Eichinger ◽  
R Bauer
Keyword(s):  
Gut Microbiota ◽  
In Vitro Study ◽  
Vitro Study ◽  
Bark Extract ◽  
Herbal Extracts ◽  
Human Gut ◽  
Human Gut Microbiota ◽  
Willow Bark

Metabolization of the herbal combination STW-5 by human gut microbiota in vitro

2017 ◽  
Author(s):  
EM Pferschy-Wenzig ◽  
A Roßmann ◽  
K Koskinen ◽  
H Abdel-Aziz ◽  
C Moissl-Eichinger ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Human Gut ◽  
Human Gut Microbiota

scholarly journals Integrating Biosensors in Organs-on-Chip Devices: A Perspective on Current Strategies to Monitor Microphysiological Systems

Biosensors ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 110 ◽  
Author(s):  
Erika Ferrari ◽  
Cecilia Palma ◽  
Simone Vesentini ◽  
Paola Occhetta ◽  
Marco Rasponi
Keyword(s):  
Imaging Techniques ◽  
Biological Models ◽  
Electromechanical Properties ◽  
Human Organs ◽  
Tissue Constructs ◽  
Microphysiological Systems ◽  
Metabolic Activities ◽  
On Chip ◽  
Chip Analysis

Organs-on-chip (OoC), often referred to as microphysiological systems (MPS), are advanced in vitro tools able to replicate essential functions of human organs. Owing to their unprecedented ability to recapitulate key features of the native cellular environments, they represent promising tools for tissue engineering and drug screening applications. The achievement of proper functionalities within OoC is crucial; to this purpose, several parameters (e.g., chemical, physical) need to be assessed. Currently, most approaches rely on off-chip analysis and imaging techniques. However, the urgent demand for continuous, noninvasive, and real-time monitoring of tissue constructs requires the direct integration of biosensors. In this review, we focus on recent strategies to miniaturize and embed biosensing systems into organs-on-chip platforms. Biosensors for monitoring biological models with metabolic activities, models with tissue barrier functions, as well as models with electromechanical properties will be described and critically evaluated. In addition, multisensor integration within multiorgan platforms will be further reviewed and discussed.

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