Development of model of exosome transport in microfluidic gut-brain axis-on-a-chip.

The gut communicates with the brain in a variety of ways known as the gut-brain axis (GBA), which is known to affect neurophysiological functions as well as neuronal disorders. Exosomes capable of passing through the blood-brain-barrier (BBB) have received attention as a mediator of gut-brain signaling and drug delivery vehicles. In conventional well plate-based experiments, it is difficult to observe the exosome movement in real time.

Microfluidic gut-axis-on-a-chip models for pharmacokinetic-based disease models.

The low success rate of new drugs transitioning from animal testing to human clinical trials necessitates the development of more accurate and representative models. Recent advances in multi-organ-on-a-chip technology offer promising avenues for studying complex organ-organ interactions. Gut-liver-on-a-chip systems hold particular promise for mimicking the intricate interplay between the gut and liver, which play crucial roles in nutrient absorption, drug metabolism, detoxification, and immune response.

Recent Advances in Gut- and Gut-Organ-Axis-on-a-Chip Models.

The human gut extracts nutrients from the diet while forming the largest barrier against the outer environment. In addition, the gut actively maintains homeostasis through intricate interactions with the gut microbes, the immune system, the enteric nervous system, and other organs. These interactions influence digestive health and, furthermore, play crucial roles in systemic health and disease.

Recent advances in in vitro skin-on-a-chip models for drug testing.

Introduction: The skin is an organ that has the largest surface area and provides a barrier against external environment. While providing protection, it also interacts with other organs in the body and has implications for various diseases. Development of physiologically realistic models of the skin in the context of the whole body is important for studying these diseases and will be a valuable tool for pharmaceutical, cosmetics, and food industry.

Multiorgan-on-a-chip for realization of gut-skin axis.

The concept of physiological link between the gut and the skin, known as the gut-skin axis, has been gaining more evidence recently. Although experimental data from animal and human studies support the existence of the gut-skin axis, in vitro model platforms that can test the hypothesis are lacking. Organ-on-a-chip offers the possibility of connecting different tissues and recapitulating interactions between them.

Organ-on-a-Chip for Studying Gut-Brain Interaction Mediated by Extracellular Vesicles in the Gut Microenvironment.

Extracellular vesicles (EVs) are a group of membrane vesicles that play important roles in cell-to-cell and interspecies/interkingdom communications by modulating the pathophysiological conditions of recipient cells. Recent evidence has implied their potential roles in the gut-brain axis (GBA), which is a complex bidirectional communication system between the gut environment and brain pathophysiology. Despite the evidence, the roles of EVs in the gut microenvironment in the GBA are less highlighted.

Gut-Kidney Axis on Chip for Studying Effects of Antibiotics on Risk of Hemolytic Uremic Syndrome by Shiga Toxin-Producing .

Shiga toxin-producing (STEC) infects humans by colonizing the large intestine, and causes kidney damage by secreting Shiga toxins (Stxs). The increased secretion of Shiga toxin 2 (Stx2) by some antibiotics, such as ciprofloxacin (CIP), increases the risk of hemolytic-uremic syndrome (HUS), which can be life-threatening. However, previous studies evaluating this relationship have been conflicting, owing to the low frequency of EHEC infection, very small number of patients, and lack of an appropriate animal model.

Microtechnology-based models: Mimicking liver function and pathophysiology.

The liver plays important roles in drug metabolism and homeostasis. The metabolism and biotransformation can not only affect the efficacy of drugs but also result in hepatotoxicity and drug-induced liver injury. Understanding the complex physiology of the liver and the pathogenetic mechanisms of liver diseases is essential for drug development.

Multi-organ-on-a-chip for pharmacokinetics and toxicokinetic study of drugs.

: Accurate prediction of pharmacokinetic (PK) and toxicokinetics (TK) of drugs is imperative for successful development of new pharmaceutics. Although conventional methods for predicting the PK and TK of drugs are well established, limitations still exist and more advanced chip-based platforms combined with mathematical models can help researchers overcome the limitations. : We will review recent progress in the development of multi-organ-on-a-chip platforms for predicting PK and TK of drugs, as well as mathematical approaches that can be combined with these platforms for experiment design, data analysis and extrapolation (IVIVE) for application to humans.

In vitro hepatic steatosis model based on gut-liver-on-a-chip.

Hepatic steatosis, also known as fatty liver disease, occurs due to abnormal lipid accumulation in the liver. It has been known that gut absorption also plays an important role in the mechanism underlying hepatic steatosis. Conventional in vitro cell culture models have limitations in recapitulating the mechanisms of hepatic steatosis because it does not include the gut absorption process.

Three-tissue microphysiological system for studying inflammatory responses in gut-liver Axis.

The interaction between the gut and the liver, often known as the gut-liver axis, play crucial roles in modulating the body's responses to the xenobiotics as well as progression of diseases. Dysfunction of the axis can cause metabolic disorders as well as obesity, diabetes, and fatty liver disease. During the progression of such diseases, inflammatory responses involving the immune system also play an important part.

A body-on-a-chip (BOC) system for studying gut-liver interaction.

Current in vitro model systems cannot recapitulate the complex interactions between multiple organs in the body, and the whole-body responses to drugs involving multiple organs. In addition, many diseases arise from a mechanism involving multiple organs, making it difficult to build realistic models of such diseases. Organ-on-a-chip technology offers an opportunity to mimic physiological microenvironment of in vivo tissues, as well as to reproduce interactions between organs by connecting these "organ modules.

Microfluidic skin chip with vasculature for recapitulating the immune response of the skin tissue.

There is a considerable need for cell-based in vitro skin models for studying dermatological diseases and testing cosmetic products, but current in vitro skin models lack physiological relevance compared to human skin tissue. For example, many dermatological disorders involve complex immune responses, but current skin models are not capable of recapitulating the phenomena. Previously, we reported development of a microfluidic skin chip with a vessel structure and vascular endothelial cells.

Microphysiological systems for recapitulating physiology and function of blood-brain barrier.

Central nervous system (CNS) diseases are emerging as a major issue in an aging society. Although extensive research has focused on the development of CNS drugs, the limited transport of therapeutic agents across the blood-brain barrier (BBB) remains a major challenge. Conventional two-dimensional culture dishes do not recapitulate in vivo physiology and real-time observations of molecular transport are not possible in animal models.

Pharmacokinetic and pharmacodynamic insights from microfluidic intestine-on-a-chip models.

: After administration, a drug undergoes absorption, distribution, metabolism, and elimination (ADME) before exerting its effect on the body. The combination of these process yields the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of a drug. Although accurate prediction of PK and PD profiles is essential for drug development, conventional in vitro models are limited by their lack of physiological relevance.

Construction of pancreas-muscle-liver microphysiological system (MPS) for reproducing glucose metabolism.

Although in vitro models are widely accepted experimental platforms, their physiological relevance is often severely limited. The limitation of current in vitro models is strongly manifested in case of diseases where multiple organs are involved, such as diabetes and metabolic syndrome. Microphysiological systems (MPS), also known as organ-on-a-chip technology, enable a closer approximation of the human organs and tissues, by recreating the tissue microenvironment.

Application of chemical reaction engineering principles to 'body-on-a-chip' systems.

The combination of cell culture models with microscale technology has fostered emergence of cell-based microphysiological models, also known as organ-on-a-chip systems. Body-on-a-chip systems, which are multi-organ systems on a chip to mimic physiological relations, enable recapitulation of organ-organ interactions and potentially whole-body response to drugs, as well as serve as models of diseases. Chemical reaction engineering principles can be applied to understanding complex reactions inside the cell or human body, which can be treated as a multi-reactor system.

Strategies for using mathematical modeling approaches to design and interpret multi-organ microphysiological systems (MPS).

Recent advances in organ-on-a-chip technology have resulted in numerous examples of microscale systems that faithfully mimic the physiology and pathology of human organs and diseases. The next step in this field, which has already been partially demonstrated at a proof-of-concept level, would be integration of organ modules to construct multiorgan microphysiological systems (MPSs). In particular, there is interest in "body-on-a-chip" models, which recapitulate complex and dynamic interactions between different organs.

A microfluidic chip with gravity-induced unidirectional flow for perfusion cell culture.

Perfusion flow is one of the essential elements and advantages of organ-on-a-chip technology. For example, microfluidics have enabled implementation of perfusion flow and recapitulation of fluidic environment for vascular endothelial cells. The most prevalent method of implementing flow in a chip is to use a pump, which requires elaborate manipulation and complex connections, and accompanies a large amount of dead volume.

Pharmacokinetic-based multi-organ chip for recapitulating organ interactions.

Organ-on-a-chip technology provides a novel in vitro platform with a possibility of reproducing physiological functions of in vivo tissue, more accurately than conventional cell-based model systems. Many newly arising diseases result from complex interaction between multiple organs. By realizing different organ functions on a chip, organ-on-a-chip technology is a potentially useful for building models of such complex diseases.

Gut-liver on a chip toward an in vitro model of hepatic steatosis.

Hepatic steatosis is a process of abnormal lipid deposition within the liver cells, often caused by excessive alcohol uptake or obesity. A conventional in vitro model for hepatic steatosis uses a liver cell culture, treated with fatty acids and measures accumulation of lipids within the cells. This model does not recapitulate the complex process of absorption and metabolism of digestive lipids.

3D gut-liver chip with a PK model for prediction of first-pass metabolism.

Accurate prediction of first-pass metabolism is essential for improving the time and cost efficiency of drug development process. Here, we have developed a microfluidic gut-liver co-culture chip that aims to reproduce the first-pass metabolism of oral drugs. This chip consists of two separate layers for gut (Caco-2) and liver (HepG2) cell lines, where cells can be co-cultured in both 2D and 3D forms.

Inhibition of Cholesterol Synthesis in HepG2 Cells by GINST-Decreasing HMG-CoA Reductase Expression Via AMP-Activated Protein Kinase.

Unlabelled: GINST, a hydrolyzed ginseng extract, has been reported to have antidiabetic effects and to reduce hyperglycemia and hyperlipidemia. Hypercholesterolemia is caused by diet or genetic factors and can lead to atherosclerosis and coronary heart disease. Thus, the purpose of this study is to determine whether GINST and the ginsenoside metabolite, IH-901 (compound K), reduce cholesterol synthesis in HepG2 cells and the signal transduction pathways involved.

Pectinase-treated protects against chronic intermittent heat stress-induced testicular damage by modulating hormonal and spermatogenesis-related molecular expression in rats.

Background: Elevated testicular temperature disrupts spermatogenesis and causes infertility. In the present study, the protective effect of enzymatically biotransformed Meyer by pectinase (GINST) against chronic intermittent heat stress-induced testicular damage in rats was investigated.

Methods: Male Sprague-Dawley rats (4 wk old, 60-70 g) were divided into four groups: normal control (NC), heat-stress control (HC), heat-stress plus GINST-100 mg/kg (HG100), and heat-stress plus GINST-200 mg/kg (HG200) treatment groups.