The translational roadmap of the gut models, focusing on gut-on-chip

It is difficult to model in vitro the intestine when seeking to include crosstalk with the gut microbiota, immune and neuroendocrine systems. Here we present a roadmap of the current models to facilitate the choice in preclinical and translational research with a focus on gut-on-chip. These micro physiological systems (MPS) are microfluidic devices that recapitulate in vitro the physiology of the intestine. We reviewed the gut-on-chips that had been developed in academia and industries as single chip and that have three main purpose: replicate the intestinal physiology, the intestinal pathological features, and for pharmacological tests.

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The Tumor-on-Chip: Recent Advances in the Development of Microfluidic Systems to Recapitulate the Physiology of Solid Tumors

Materials ◽

10.3390/ma12182945 ◽

2019 ◽

Vol 12 (18) ◽

pp. 2945 ◽

Cited By ~ 10

Author(s):

Grissel Trujillo-de Santiago ◽

Brenda Giselle Flores-Garza ◽

Jorge Alfonso Tavares-Negrete ◽

Itzel Montserrat Lara-Mayorga ◽

Ivonne González-Gamboa ◽

...

Keyword(s):

Cancer Research ◽

Solid Tumors ◽

3D Culture ◽

Microfluidic Devices ◽

Pharmaceutical Compounds ◽

Microfluidic Systems ◽

Cancer Etiology ◽

Culture Systems ◽

On Chip

The ideal in vitro recreation of the micro-tumor niche—although much needed for a better understanding of cancer etiology and development of better anticancer therapies—is highly challenging. Tumors are complex three-dimensional (3D) tissues that establish a dynamic cross-talk with the surrounding tissues through complex chemical signaling. An extensive body of experimental evidence has established that 3D culture systems more closely recapitulate the architecture and the physiology of human solid tumors when compared with traditional 2D systems. Moreover, conventional 3D culture systems fail to recreate the dynamics of the tumor niche. Tumor-on-chip systems, which are microfluidic devices that aim to recreate relevant features of the tumor physiology, have recently emerged as powerful tools in cancer research. In tumor-on-chip systems, the use of microfluidics adds another dimension of physiological mimicry by allowing a continuous feed of nutrients (and pharmaceutical compounds). Here, we discuss recently published literature related to the culture of solid tumor-like tissues in microfluidic systems (tumor-on-chip devices). Our aim is to provide the readers with an overview of the state of the art on this particular theme and to illustrate the toolbox available today for engineering tumor-like structures (and their environments) in microfluidic devices. The suitability of tumor-on-chip devices is increasing in many areas of cancer research, including the study of the physiology of solid tumors, the screening of novel anticancer pharmaceutical compounds before resourcing to animal models, and the development of personalized treatments. In the years to come, additive manufacturing (3D bioprinting and 3D printing), computational fluid dynamics, and medium- to high-throughput omics will become powerful enablers of a new wave of more sophisticated and effective tumor-on-chip devices.

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Protein degradation analysis by affinity microfluidics

10.1101/2021.10.13.464189 ◽

2021 ◽

Author(s):

Lev Brio ◽

Danit Wasserman ◽

Efrat Michaely-Barbiro ◽

Doron Gerber ◽

Amit Tzur

Keyword(s):

Protein Degradation ◽

Translational Research ◽

Polyacrylamide Gel Electrophoresis ◽

Minute Amount ◽

Cellular Processes ◽

Degradation Analysis ◽

Ubiquitin Proteasome ◽

Proteasome Pathway ◽

On Chip

Protein degradation mediated by the ubiquitin-proteasome pathway regulates signaling events in all eukaryotic cells, with implications in pathological conditions such as cancer and neurodegenerative diseases. Detection of protein degradation is an elementary need in basic and translational research. In vitro degradation assays, in particular, have been instrumental in the understanding of how cell proliferation and other fundamental cellular processes are regulated. These assays are direct, quantitative and highly informative but also laborious, typically relying on low-throughput polyacrylamide gel-electrophoresis followed by autoradiography or immunoblotting. We present protein degradation on chip (pDOC), a MITOMI-based integrated microfluidic device for discovery and analysis of ubiquitin mediated proteolysis. The platform accommodates microchambers on which protein degradation is assayed quickly and simultaneously in physiologically relevant environments, using minute amount of reagents. Essentially, pDOC provides a multiplexed, sensitive and colorimetric alternative to the conventional degradation assays, with relevance to biomedical and translational research.

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Organ-on-a-Chip: New Platform for Biological Analysis

Analytical Chemistry Insights ◽

10.4137/aci.s28905 ◽

2015 ◽

Vol 10 ◽

pp. ACI.S28905 ◽

Cited By ~ 27

Author(s):

Fan An ◽

Yueyang Qu ◽

Xianming Liu ◽

Runtao Zhong ◽

Yong Luo

Keyword(s):

Mammalian Cell ◽

Direct Detection ◽

Microfluidic Devices ◽

Fast Evaluation ◽

Multiple Functions ◽

The Past ◽

Organ On A Chip ◽

On Chip ◽

Detection Schemes

Direct detection and analysis of biomolecules and cells in physiological microenvironment is urgently needed for fast evaluation of biology and pharmacy. The past several years have witnessed remarkable development opportunities in vitro organs and tissues models with multiple functions based on microfluidic devices, termed as “organ-on-a-chip”. Briefly speaking, it is a promising technology in rebuilding physiological functions of tissues and organs, featuring mammalian cell co-culture and artificial microenvironment created by microchannel networks. In this review, we summarized the advances in studies of heart-, vessel-, liver-, neuron-, kidney- and Multi-organs-on-a-chip, and discussed some noteworthy potential on-chip detection schemes.

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How Microgels Can Improve the Impact of Organ-on-Chip and Microfluidic Devices for 3D Culture: Compartmentalization, Single Cell Encapsulation and Control on Cell Fate

Polymers ◽

10.3390/polym13193216 ◽

2021 ◽

Vol 13 (19) ◽

pp. 3216

Author(s):

Simona Argentiere ◽

Pietro Aleardo Siciliano ◽

Laura Blasi

Keyword(s):

Cell Fate ◽

3D Culture ◽

Cell Encapsulation ◽

Microfluidic Devices ◽

Future Research ◽

Hydrogel Matrix ◽

Cellular Microenvironments ◽

On Chip ◽

The Impact

The Organ-on-chip (OOC) devices represent the new frontier in biomedical research to produce micro-organoids and tissues for drug testing and regenerative medicine. The development of such miniaturized models requires the 3D culture of multiple cell types in a highly controlled microenvironment, opening new challenges in reproducing the extracellular matrix (ECM) experienced by cells in vivo. In this regard, cell-laden microgels (CLMs) represent a promising tool for 3D cell culturing and on-chip generation of micro-organs. The engineering of hydrogel matrix with properly balanced biochemical and biophysical cues enables the formation of tunable 3D cellular microenvironments and long-term in vitro cultures. This focused review provides an overview of the most recent applications of CLMs in microfluidic devices for organoids formation, highlighting microgels’ roles in OOC development as well as insights into future research.

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

Planta Medica ◽

10.1055/s-0036-1596386 ◽

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

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

10.1055/s-0037-1608399 ◽

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

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Review of Microfluidic Devices for On-Chip Chemical Sensing

IEEJ Transactions on Sensors and Micromachines ◽

10.1541/ieejsmas.136.244 ◽

2016 ◽

Vol 136 (6) ◽

pp. 244-249

Author(s):

Takahiro Watanabe ◽

Fumihiro Sassa ◽

Yoshitaka Yoshizumi ◽

Hiroaki Suzuki

Keyword(s):

Chemical Sensing ◽

Microfluidic Devices ◽

On Chip

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

Biosensors ◽

10.3390/bios10090110 ◽

2020 ◽

Vol 10 (9) ◽

pp. 110 ◽

Cited By ~ 2

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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Preservation of Human Gut Microbiota Inoculums for In Vitro Fermentations Studies

Fermentation ◽

10.3390/fermentation7010014 ◽

2021 ◽

Vol 7 (1) ◽

pp. 14

Author(s):

Nelson Mota de Carvalho ◽

Diana Luazi Oliveira ◽

Mayra Anton Dib Saleh ◽

Manuela Pintado ◽

Ana Raquel Madureira

Keyword(s):

Gut Microbiota ◽

Metabolic Profile ◽

Bacterial Count ◽

Glycerol Solution ◽

Metabolic Profiles ◽

Human Gut ◽

Colonic Fermentation ◽

In Vitro Fermentation ◽

Fecal Samples

The use of fecal inoculums for in vitro fermentation models requires a viable gut microbiota, capable of fermenting the unabsorbed nutrients. Fresh samples from human donors are used; however, the availability of fresh fecal inoculum and its inherent variability is often a problem. This study aimed to optimize a method of preserving pooled human fecal samples for in vitro fermentation studies. Different conditions and times of storage at −20 °C were tested. In vitro fermentation experiments were carried out for both fresh and frozen inoculums, and the metabolic profile compared. In comparison with the fresh, the inoculum frozen in a PBS and 30% glycerol solution, had a significantly lower (p < 0.05) bacterial count (<1 log CFU/mL). However, no significant differences (p < 0.05) were found between the metabolic profiles after 48 h. Hence, a PBS and 30% glycerol solution can be used to maintain the gut microbiota viability during storage at −20 °C for at least 3 months, without interfering with the normal course of colonic fermentation.

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The gut microbiome of laboratory mice: considerations and best practices for translational research

Mammalian Genome ◽

10.1007/s00335-021-09863-7 ◽

2021 ◽

Author(s):

Aaron C. Ericsson ◽

Craig L. Franklin

Keyword(s):

Human Physiology ◽

Best Practices ◽

Gut Microbiota ◽

Translational Research ◽

Mouse Models ◽

Gut Microbiome ◽

Predictive Power ◽

Environmental Influences ◽

Pharmacological Intervention ◽

Laboratory Mice

AbstractJust as the gut microbiota (GM) is now recognized as an integral mediator of environmental influences on human physiology, susceptibility to disease, and response to pharmacological intervention, so too does the GM of laboratory mice affect the phenotype of research using mouse models. Multiple experimental factors have been shown to affect the composition of the GM in research mice, as well as the model phenotype, suggesting that the GM represents a major component in experimental reproducibility. Moreover, several recent studies suggest that manipulation of the GM of laboratory mice can substantially improve the predictive power or translatability of data generated in mouse models to the human conditions under investigation. This review provides readers with information related to these various factors and practices, and recommendations regarding methods by which issues with poor reproducibility or translatability can be transformed into discoveries.

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