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Many patients infected with coronaviruses, such as SARS-CoV-2 and NL63 that use ACE2 receptors to infect cells, exhibit gastrointestinal symptoms and viral proteins are found in the human gastrointestinal tract, yet little is known about the inflammatory and pathological effects of coronavirus infection on the human intestine. Here, we used a human intestine-on-a-chip (Intestine Chip) microfluidic culture device lined by patient organoid-derived intestinal epithelium interfaced with human vascular endothelium to study host cellular and inflammatory responses to infection with NL63 coronavirus. These organoid-derived intestinal epithelial cells dramatically increased their ACE2 protein levels when cultured under flow in the presence of peristalsis-like mechanical deformations in the Intestine Chips compared to when cultured statically as organoids or in Transwell inserts. Infection of the intestinal epithelium with NL63 on-chip led to inflammation of the endothelium as demonstrated by loss of barrier function, increased cytokine production, and recruitment of circulating peripheral blood mononuclear cells (PBMCs). Treatment of NL63 infected chips with the approved protease inhibitor drug, nafamostat, inhibited viral entry and resulted in a reduction in both viral load and cytokine secretion, whereas remdesivir, one of the few drugs approved for COVID19 patients, was not found to be effective and it also was toxic to the endothelium. This model of intestinal infection was also used to test the effects of other drugs that have been proposed for potential repurposing against SARS-CoV-2. Taken together, these data suggest that the human Intestine Chip might be useful as a human preclinical model for studying coronavirus related pathology as well as for testing of potential anti-viral or anti-inflammatory therapeutics.

Many patients infected with coronaviruses, such as SARS-CoV-2 and NL63 that use ACE2 receptors to infect cells, exhibit gastrointestinal symptoms and viral proteins are found in the human gastrointestinal tract, yet little is known about the inflammatory and pathological effects of coronavirus infection on the human intestine. Here, we used a human intestine-on-a-chip (Intestine Chip) microfluidic culture device lined by patient organoid-derived intestinal epithelium interfaced with human vascular endothelium to study host cellular and inflammatory responses to infection with NL63 coronavirus. These organoid-derived intestinal epithelial cells dramatically increased their ACE2 protein levels when cultured under flow in the presence of peristalsis-like mechanical deformations in the Intestine Chips compared to when cultured statically as organoids or in Transwell inserts. Infection of the intestinal epithelium with NL63 on-chip led to inflammation of the endothelium as demonstrated by loss of barrier function, increased cytokine production, and recruitment of circulating peripheral blood mononuclear cells (PBMCs). Treatment of NL63 infected chips with the approved protease inhibitor drug, nafamostat, inhibited viral entry and resulted in a reduction in both viral load and cytokine secretion, whereas remdesivir, one of the few drugs approved for COVID19 patients, was not found to be effective and it also was toxic to the endothelium. This model of intestinal infection was also used to test the effects of other drugs that have been proposed for potential repurposing against SARS-CoV-2. Taken together, these data suggest that the human Intestine Chip might be useful as a human preclinical model for studying coronavirus related pathology as well as for testing of potential anti-viral or anti-inflammatory therapeutics. [ABSTRACT FROM AUTHOR]

One of the major challenges we face as humankind is supplying a growing world population with sufficient and healthy foods. Although from a worldwide perspective sufficient food is produced, locally, the situation can be dire. Furthermore, the production needs to be increased in a sustainable manner for future generations, which also implies prevention of food waste, and making better use of the available resources. How to contribute to this as food technologists is an ultimate question, especially since the tools that can investigate processes at relevant time scales, and dimensions, are lacking. Here we propose the use of microtechnology and show examples of how this has led to new insights in the fields of ingredient isolation (filtration), and emulsion/foam formation, which will ultimately lead to better-defined products. Furthermore, microfluidic tools have been applied for testing ingredient functionality, and for this, various examples are discussed that will expectedly contribute to making better use of more sustainably sourced starting materials (e.g., novel protein sources). This review will wrap up with a section in which we discuss future developments. We expect that it will be possible to link food properties to the effects that foods create in vivo. We thus expand the scope of this review that is technical in nature, toward physiological functionality, and ultimately to rational food design that is targeted to improve human health. [ABSTRACT FROM AUTHOR]

INTRODUCTION: This talk will discuss the applications of tissue engineering in two areas of medicine: regenerative engineering of whole organs at the clinical scale, and modelling of diseases and therapeutic modalities using microsized “organs on chip” platforms. EXPERIMENTAL: Engineering of human tissues involves the use of human stem cells (in most cases derived from a sample of blood) and two engineering components that are “instructing” the cells how to form a specific tissue. Th first component is a tissue specific biomaterial scaffold that serves as a structural and logistic template for tissue formation. The second component is the bioreactor designed to provide homeostasis and tissue-specific molecular and physical regulatory factors, as well as sensing and imaging modalities necessary to monitor and measure tissue development and function. In all cases, we aim to recapitulate the cell niches, using bioengineering tools. RESULTS AND DISCUSSION: To illustrate the state of the art in the field and reflect on the current challenges and opportunities, this talk will discuss representative examples of whole organ engineering and organs-on chip models of injury, disease and regeneration. At the clinical scale, the goal is to achieve regeneration by treating the whole organ damaged by injury of disease. We will discuss regenerative engineering of a joint (that can be engineered de novo), and the lung and heart (that are being regenerated with the use of therapeutic cells). In organs-on-chip platforms, microsized human tissues are matured to adult-like phenotypes and functionally linked by vascular perfusion containing circulating cells and factors. At the micro-scale, we will focus on organs on chip models of cancer metastasis, radiation damage, and side effects of some common drugs. Finally, we will discuss the key challenges the field is currently facing. CONCLUSIONS: Tissue engineering is increasingly successful in recapitulating human physiology in health and disease, in patient-specific settings, supporting the development of high-fidelity research models and treatment modalities tailored to the specific patient. [ABSTRACT FROM AUTHOR]

Cosmic radiation is the most serious risk that will be encountered during the planned missions to the Moon and Mars. There is a compelling need to understand the effects, safety thresholds, and mechanisms of radiation damage in human tissues, in order to develop measures for radiation protection during extended space travel. As animal models fail to recapitulate the molecular changes in astronauts, engineered human tissues and "organs-on-chips" are valuable tools for studying effects of radiation in vitro. We have developed a bioengineered tissue platform for studying radiation damage in individualized settings. To demonstrate its utility, we determined the effects of radiation using engineered models of two human tissues known to be radiosensitive: engineered cardiac tissues (eCT, a target of chronic radiation damage) and engineered bone marrow (eBM, a target of acute radiation damage). We report the effects of high-dose neutrons, a proxy for simulated galactic cosmic rays, on the expression of key genes implicated in tissue responses to ionizing radiation, phenotypic and functional changes in both tissues, and proof-of-principle application of radioprotective agents. We further determined the extent of inflammatory, oxidative stress, and matrix remodeling gene expression changes, and found that these changes were associated with an early hypertrophic phenotype in eCT and myeloid skewing in eBM. We propose that individualized models of human tissues have potential to provide insights into the effects and mechanisms of radiation during deep-space missions and allow testing of radioprotective measures. One Sentence Summary: Engineered human tissue models can be used to study and counter the effects of cosmic radiation. [ABSTRACT FROM AUTHOR]

The Safety Pharmacology Society (SPS) held a Northeast (NE) regional meeting in Boston, MA on May 13, 2016 at the Vertex Pharmaceuticals Incorporated site. There were 103 attendees from the pharmaceutical industry, contract research organizations (CROs), academia, and global regulatory agencies. An assortment of scientific topics were presented by 7 speakers that included broad topics in the cardiovascular (organ on chip, statistical power and translation of rat cardiovascular telemetry data and dual inhibition of I Kr and I Ks on QT interval prolongation) and central nervous system (in vitro platform for neurotoxicity, an integrated risk assessment of suicidal ideation and behavior, and EEG advances in safety pharmacology) and a novel topic discussing preclinical challenges faced in the development of a novel gene therapy. A highlight of the meeting was an in-depth discussion on the fatty acid acyl hydrolase (FAAH) inhibitor BIA 10-2474 which involved a comprehensive overview of the biology and pharmacology of FAAH followed by a presentation from the Biotrial (Rennes, France) team that conducted the clinical trial. An additional poster session was held that included 13 fascinating posters on cutting edge safety pharmacology topics. [ABSTRACT FROM AUTHOR]