A three-dimensional immunocompetent intestine-on-chip model as in vitro platform for functional and microbial interaction studies

Maurer, Michelle; Gresnigt, Mark S.; Wollny, Tony; Berlinghof, Florian; Pospich, Rebecca; Cseresnyés, Zoltán; Medyukhina, Anna; Graf, Katja; Gröger, Marko; Raasch, Martin; Siwczak, Fatina; Nietzsche, Sándor; Jacobsen, Ilse D.; Figge, Marc Thilo; Hube, Bernhard; Huber, Otmar; Mosig, Alexander S.

doi:10.1016/j.biomaterials.2019.119396

Cited by 139 publications

(132 citation statements)

References 64 publications

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“…Scanning electron microscopy. The fixation of the cells was performed inside the human alveolus-on-a-chip model by using the same fixative as for TEM for 60 min at room temperature as described previously (Deinhardt-Emmer et al, 2020a;Maurer et al, 2019;Rennert et al, 2015). Afterwards, the chips were rinsed three times with fresh cacodylate buffer for 10 min each and the membranes were cut out.…”

Section: Methodsmentioning

confidence: 99%

SARS-CoV-2 causes severe alveolar inflammation and barrier dysfunction

Deinhardt‐Emmer

Böttcher

Haring

et al. 2020

Preprint

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Infections with SARS-CoV-2 lead to mild to severe coronavirus disease-19 (COVID-19) with systemic symptoms. Although the viral infection originates in the respiratory system, it is unclear how the virus can overcome the alveolar barrier, which is observed in severe COVID-19 disease courses.To elucidate the viral effects on the barrier integrity and immune reactions, we used mono-cell culture systems and a complex human alveolus-on-a-chip model composed of epithelial, endothelial, and mononuclear cells.Our data show that SARS-CoV-2 efficiently infected epithelial cells with high viral loads and inflammatory response, including the interferon expression. By contrast, the adjacent endothelial layer was no infected and did neither show productive virus replication or interferon release. With prolonged infection, both cell types are damaged, and the barrier function is deteriorated, allowing the viral particles to overbear.In our study, we demonstrate that although SARS-CoV-2 is dependent on the epithelium for efficient replication, the neighboring endothelial cells are affected, e.g., by the epithelial cytokine release, which results in the damage of the alveolar barrier function and viral dissemination.

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Section: Methodsmentioning

confidence: 99%

SARS-CoV-2 causes severe alveolar inflammation and barrier dysfunction

Deinhardt‐Emmer

Böttcher

Haring

et al. 2020

Preprint

Self Cite

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“…Another study using an intestinal chip model demonstrated that LPS disrupted the intestinal barrier and that lactobacillus was able to protect against the invasion across the epithelium of the opportunistic pathogen Candida albicans in this model ( Maurer et al, 2019 ). Another model of enterohemorrhagic E. coli (EHEC) infection, a pathogenic bacterium causing diarrheal illness, showed that addition of specific metabolites from the gut microbiome potentiate the pathogen’s infection, providing a potential explanation for why certain organisms (e.g., mice) and certain human subpopulations (e.g., children) may have different susceptibilities to EHEC ( Tovaglieri et al, 2019 ).…”

Section: Microfluidic “Organ-on-a-chip” Models Of the Intestinementioning

confidence: 99%

Human Microphysiological Models of Intestinal Tissue and Gut Microbiome

Steinway

Saleh

Koo

et al. 2020

Front. Bioeng. Biotechnol.

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The gastrointestinal (GI) tract is a complex system responsible for nutrient absorption, digestion, secretion, and elimination of waste products that also hosts immune surveillance, the intestinal microbiome, and interfaces with the nervous system. Traditional in vitro systems cannot harness the architectural and functional complexity of the GI tract. Recent advances in organoid engineering, microfluidic organs-on-a-chip technology, and microfabrication allows us to create better in vitro models of human organs/tissues. These micro-physiological systems could integrate the numerous cell types involved in GI development and physiology, including intestinal epithelium, endothelium (vascular), nerve cells, immune cells, and their interplay/cooperativity with the microbiome. In this review, we report recent progress in developing microphysiological models of the GI systems. We also discuss how these models could be used to study normal intestinal physiology such as nutrient absorption, digestion, and secretion as well as GI infection, inflammation, cancer, and metabolism.

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“…Integrating patient-specific or hiPSC-derived intestinal 3D cell constructs, local immune cells, pathogens, and the commensal microbiota into OoCs might create a highly defined and controllable translation platform that should accelerate the discovery of new drugs and/or personalized precision probiotic therapeutics. Maurer et al have established a 3D immunocompetent intestine-on-a-chip model as an in vitro platform for functional and microbial interaction studies [221]. This model allows for a detailed characterization of the immune response, microbial pathogenicity mechanisms, and quantification of cellular dysfunction attributed to alterations in the microbial composition.…”

Section: Organs-on-a-chip/microphysiological Systemsmentioning

confidence: 99%

Links between Nutrition, Infectious Diseases, and Microbiota: Emerging Technologies and Opportunities for Human-Focused Research

et al. 2020

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The interaction between nutrition and human infectious diseases has always been recognized. With the emergence of molecular tools and post-genomics, high-resolution sequencing technologies, the gut microbiota has been emerging as a key moderator in the complex interplay between nutrients, human body, and infections. Much of the host–microbial and nutrition research is currently based on animals or simplistic in vitro models. Although traditional in vivo and in vitro models have helped to develop mechanistic hypotheses and assess the causality of the host–microbiota interactions, they often fail to faithfully recapitulate the complexity of the human nutrient–microbiome axis in gastrointestinal homeostasis and infections. Over the last decade, remarkable progress in tissue engineering, stem cell biology, microfluidics, sequencing technologies, and computing power has taken place, which has produced a new generation of human-focused, relevant, and predictive tools. These tools, which include patient-derived organoids, organs-on-a-chip, computational analyses, and models, together with multi-omics readouts, represent novel and exciting equipment to advance the research into microbiota, infectious diseases, and nutrition from a human-biology-based perspective. After considering some limitations of the conventional in vivo and in vitro approaches, in this review, we present the main novel available and emerging tools that are suitable for designing human-oriented research.

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A three-dimensional immunocompetent intestine-on-chip model as in vitro platform for functional and microbial interaction studies

Cited by 139 publications

References 64 publications

SARS-CoV-2 causes severe alveolar inflammation and barrier dysfunction

SARS-CoV-2 causes severe alveolar inflammation and barrier dysfunction

Human Microphysiological Models of Intestinal Tissue and Gut Microbiome

Links between Nutrition, Infectious Diseases, and Microbiota: Emerging Technologies and Opportunities for Human-Focused Research

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