scholarly journals A Gut-Brain Axis-on-a-Chip for studying transport across epithelial and endothelial barriers

2021 ◽  
Author(s):  
Min-Hyeok Kim ◽  
Donghyun Kim ◽  
Jong Hwan Sung
Keyword(s):  
Cognitive Abilities ◽  
In Vitro Model ◽  
Commensal Microbiota ◽  
Cell Responses ◽  
Chip Technology ◽  
Endothelial Barriers ◽  
Dietary Components ◽  
Vitro Model ◽  
The Brain

Recent research on Gut-Brain Axis (GBA) has suggested that the gut luminal environment, including the dietary components and commensal microbiota, could affect behavior, emotion, and cognitive abilities in the brain. The research on GBA has heavily relied on animal models, which makes the research challenging. Recent advances in organ-on-a-chip technology could be a solution for GBA research. In present work, we developed a modular microfluidic chip, where gut epithelial and brain endothelial cells were co-cultured to form the gut epithelial barrier and the Blood-Brain Barrier (BBB). Cell responses to microbial byproducts were examined by TEER measurement for each barrier, and we observed the transport of fluorescently labeled exosome across the gut barrier towards the BBB. Our results suggest this model can be used as a novel in vitro model of GBA for studying the interaction between the gut and the brain.

In vitro model for predicting the access and distribution of drugs in the brain using hCMEC/D3 cells

2021 ◽  
Author(s):  
Bárbara Sánchez-Dengra ◽  
Isabel González-Álvarez ◽  
Flavia Sousa ◽  
Marival Bermejo ◽  
Marta González-Álvarez ◽  
...  
Keyword(s):  
In Vitro Model ◽  
Vitro Model ◽  
The Brain

scholarly journals Delivery of Thyronamines (TAMs) to the Brain: A Preliminary Study

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1616
Author(s):  
Nicoletta di Leo ◽  
Stefania Moscato ◽  
Marco Borso' ◽  
Simona Sestito ◽  
Beatrice Polini ◽  
...  
Keyword(s):  
High Performance ◽  
In Vitro Model ◽  
New Drugs ◽  
Therapeutic Approaches ◽  
Neuroprotective Effects ◽  
Pharmacological Response ◽  
Preliminary Study ◽  
Vitro Model ◽  
The Brain

Recent reports highlighted the significant neuroprotective effects of thyronamines (TAMs), a class of endogenous thyroid hormone derivatives. In particular, 3-iodothyronamine (T1AM) has been shown to play a pleiotropic role in neurodegeneration by modulating energy metabolism and neurological functions in mice. However, the pharmacological response to T1AM might be influenced by tissue metabolism, which is known to convert T1AM into its catabolite 3-iodothyroacetic acid (TA1). Currently, several research groups are investigating the pharmacological effects of T1AM systemic administration in the search of novel therapeutic approaches for the treatment of interlinked pathologies, such as metabolic and neurodegenerative diseases (NDDs). A critical aspect in the development of new drugs for NDDs is to know their distribution in the brain, which is fundamentally related to their ability to cross the blood–brain barrier (BBB). To this end, in the present study we used the immortalized mouse brain endothelial cell line bEnd.3 to develop an in vitro model of BBB and evaluate T1AM and TA1 permeability. Both drugs, administered at 1 µM dose, were assayed by high-performance liquid chromatography coupled to mass spectrometry. Our results indicate that T1AM is able to efficiently cross the BBB, whereas TA1 is almost completely devoid of this property.

scholarly journals Requirement for CD40-CD40 Ligand Interaction for Elimination of Cryptosporidium parvum from Mice

1998 ◽  
Vol 66 (2) ◽  
pp. 603-607 ◽  
Author(s):  
Mary Cosyns ◽  
Svetlana Tsirkin ◽  
Michelle Jones ◽  
Richard Flavell ◽  
Hitoshi Kikutani ◽  
...  
Keyword(s):  
Cryptosporidium Parvum ◽  
In Vitro Model ◽  
Biliary Tree ◽  
Cd40 Ligand ◽  
Ligand Interaction ◽  
Cell Responses ◽  
Infected Cells ◽  
Vitro Model

ABSTRACT Mice with disrupted genes for CD40 and CD40 ligand (CD40L) are unable to clear infection with Cryptosporidium parvum and develop cholangitis. Parasites are present in the gut, gall bladder, and biliary tree, and biliary epithelial cells express CD40 on the cell surface. SCID mice infected with C. parvum for >1 month can clear the infection after reconstitution with spleen cells from CD40, but not CD40L, knockout mice. In an in vitro model, C. parvum-infected HepG2 cells were triggered to apoptosis when incubated with a CD40L-CD8 fusion protein. The requirement for CD40-CD40L interactions for immunity to C. parvum indicated by our results may entail the triggering of apoptosis in infected cells, in addition to the known role of CD40L-CD40 interactions in stimulating cytokine production and promoting T-cell responses.

scholarly journals Autologous human immunocompetent white adipose tissue-on-chip

2021 ◽  
Author(s):  
Julia Rogal ◽  
Raylin Xu ◽  
Julia Roosz ◽  
Claudia Teufel ◽  
Madalena Cipriano ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
In Vitro Model ◽  
Molecular Mechanisms ◽  
Cell Types ◽  
Associated Diseases ◽  
Chip Technology ◽  
Vitro Model ◽  
On Chip

Obesity and associated diseases, such as diabetes, have reached epidemic proportions globally. In the era of 'diabesity' and due to its central role for metabolic and endocrine processes, adipose tissue (specifically white adipose tissue; WAT) has become a target of high interest for therapeutic strategies. To gain insights in cellular and molecular mechanisms of adipose (patho-)physiology, researchers traditionally relied on animal models since in vitro studies on human WAT are challenging due to the large size, buoyancy, and fragility of mature white adipocytes. Leveraging the Organ-on-Chip technology, we introduce a next-generation microphysiological in vitro model of human WAT based on a tailored microfluidic platform featuring vasculature-like perfusion. The platform integrates a 3D tissue comprising all major WAT-associated cellular components in an autologous manner, including not only mature adipocytes but also organotypic endothelial barriers and stromovascular cells featuring tissue-resident innate immune cells, specifically adipose tissue macrophages. This microphysiological tissue model recapitulates pivotal WAT functions, such as energy storage and mobilization as well as endocrine and immunomodulatory activities. The combination of all individual cell types with extra cellular matrix-like hydrogels in a precisely controllable bottom-up approach enables the generation of a multitude of replicates from the same donors circumventing issues of inter-donor variability and paving the way for personalized medicine. Moreover, it allows to adjust the model's degree of complexity to fit a specific purpose via a flexible mix-and-match approach with different cell component modules. This novel WAT-on-chip system constitutes a human- based, autologous and immunocompetent in vitro model of adipose tissue that recapitulates almost full tissue heterogeneity. In the future, the new WAT-on-chip model can become a powerful tool for human-relevant research in the field of metabolism and its associated diseases as well as for compound testing and personalized- and precision medicine applications.

scholarly journals Primary brain cell infection by Toxoplasma gondii reveals the extent and dynamics of parasite differentiation and impact on neuron biology.

2021 ◽  
Author(s):  
Thomas Mouveaux ◽  
Emmanuel Roger ◽  
Alioune Gueye ◽  
Fanny Eysert ◽  
Ludovic Huot ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
In Vitro Model ◽  
Brain Cell ◽  
Brain Cells ◽  
Specific Response ◽  
Cell Infection ◽  
Vitro Model ◽  
The Brain

Toxoplasma gondii is a eukaryotic parasite that form latent cyst in the brain of immunocompetent individuals. The latent parasites infection of the immune privileged central nervous system is linked to most complications. With no drug currently available to eliminate the latent cysts in the brain of infected hosts, the consequences of neurons long-term infection are unknown. It has long been known that T. gondii specifically differentiate into a latent form (bradyzoite) in neurons, but how the infected neuron is responding to the infection remain to be elucidated. We have established a new in vitro model resulting in the production of fully mature bradyzoites cysts in brain cells. Using dual, host and parasite, RNA-seq we characterized the dynamics of differentiation of the parasite, revealing the involvement of key pathways in this process. Moreover, we identified how the infected brain cells responded to the parasite infection revealing the drastic changes that take place. We showed that neuronal specific pathways are strongly affected, with synapse signaling being particularly affected, especially glutamatergic synapse. The establishment of this new in vitro model allows to investigate both the dynamics of the parasite differentiation and the specific response of neurons to the long term infection by this parasite.

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