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https://www.readbyqxmd.com/read/29262260/breaking-the-in-vitro-barrier-in-respiratory-medicine-engineered-microphysiological-systems-for-copd-and-beyond
#1
Kambez H Benam, Melanie Königshoff, Oliver Eickelberg
Chronic obstructive pulmonary disease (COPD) is a leading global health problem; however, our ability to understand the disease pathogenic processes and discover new pharmacotherapies have been significantly hindered due to lack of reliable model systems that are human-derived, physiologically more relevant, and can be applied predictively. Recent advances in microsystems engineering have made it possible to create biomimetic microfluidic cell culture devices, known as 'organs-on-chips'. In this Pulmonary Perspective, we discuss the emergence of 'Lung- and Small Airway-on-a-Chip' technologies and their application to recapitulate critical aspects of human lung pathophysiology, in particular COPD...
December 20, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/29251840/blood-brain-barrier-development-systems-modeling-and-predictive-toxicology
#2
REVIEW
Katerine S Saili, Todd J Zurlinden, Andrew J Schwab, Aymeric Silvin, Nancy C Baker, E Sidney Hunter, Florent Ginhoux, Thomas B Knudsen
The blood-brain barrier (BBB) serves as a gateway for passage of drugs, chemicals, nutrients, metabolites, and hormones between vascular and neural compartments in the brain. Here, we review BBB development with regard to the microphysiology of the neurovascular unit (NVU) and the impact of BBB disruption on brain development. Our focus is on modeling these complex systems. Extant in silico models are available as tools to predict the probability of drug/chemical passage across the BBB; in vitro platforms for high-throughput screening and high-content imaging provide novel data streams for profiling chemical-biological interactions; and engineered human cell-based microphysiological systems provide empirical models with which to investigate the dynamics of NVU function...
December 1, 2017: Birth Defects Research
https://www.readbyqxmd.com/read/29217459/technical-aspects-of-microphysiological-systems-mps-as-a-promising-wet-human-in-vivo-simulator
#3
REVIEW
Toshiyuki Kanamori, Shinji Sugiura, Yasuyuki Sakai
Microphysiological systems (MPS) are currently attracting a lot of interest from pharmaceutical companies worldwide. In the United States and European Union, several large government projects related to MPS have been initiated, and, in Japan, pharmaceutical companies interested in MPS are watching the recent trends and developments in the field. In July 2017, the Japan Agency for Medical Research and Development initiated a research program to develop chip-based MPS. In this review, we examine the technical aspects of commercializing chip-based MPS...
November 23, 2017: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/29214585/microphysiological-systems-tissue-chips-and-their-utility-for-rare-disease-research
#4
Lucie A Low, Danilo A Tagle
The scientific and technological development of microphysiological systems (MPS) modeling organs-on-chips, or "tissue chips" (TCs), has progressed rapidly over the past decade. Stem cell research and microfluidic concepts have combined to lead to the development of microphysiological platforms representing an ever-expanding list of different human organ systems. In the context of rare diseases, these bioengineered microfluidics platforms hold promise for modeling of disorders and could prove useful in the screening and efficacy testing of existing therapeutics...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29205920/multiorgan-microphysiological-systems-for-drug-development-strategies-advances-and-challenges
#5
REVIEW
Ying I Wang, Carlos Carmona, James J Hickman, Michael L Shuler
Traditional cell culture and animal models utilized for preclinical drug screening have led to high attrition rates of drug candidates in clinical trials due to their low predictive power for human response. Alternative models using human cells to build in vitro biomimetics of the human body with physiologically relevant organ-organ interactions hold great potential to act as "human surrogates" and provide more accurate prediction of drug effects in humans. This review is a comprehensive investigation into the development of tissue-engineered human cell-based microscale multiorgan models, or multiorgan microphysiological systems for drug testing...
December 4, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/29202460/human-liver-kidney-model-elucidates-the-mechanisms-of-aristolochic-acid-nephrotoxicity
#6
Shih-Yu Chang, Elijah J Weber, Viktoriya S Sidorenko, Alenka Chapron, Catherine K Yeung, Chunying Gao, Qingcheng Mao, Danny Shen, Joanne Wang, Thomas A Rosenquist, Kathleen G Dickman, Thomas Neumann, Arthur P Grollman, Edward J Kelly, Jonathan Himmelfarb, David L Eaton
Environmental exposures pose a significant threat to human health. However, it is often difficult to study toxicological mechanisms in human subjects due to ethical concerns. Plant-derived aristolochic acids are among the most potent nephrotoxins and carcinogens discovered to date, yet the mechanism of bioactivation in humans remains poorly understood. Microphysiological systems (organs-on-chips) provide an approach to examining the complex, species-specific toxicological effects of pharmaceutical and environmental chemicals using human cells...
November 16, 2017: JCI Insight
https://www.readbyqxmd.com/read/29184959/a-multi-throughput-multi-organ-on-a-chip-system-on-a-plate-formatted-pneumatic-pressure-driven-medium-circulation-platform
#7
T Satoh, S Sugiura, K Shin, R Onuki-Nagasaki, S Ishida, K Kikuchi, M Kakiki, T Kanamori
This paper reports a multi-throughput multi-organ-on-a-chip system formed on a pneumatic pressure-driven medium circulation platform with a microplate-sized format as a novel type of microphysiological system. The pneumatic pressure-driven platform enabled parallelized multi-organ experiments (i.e. simultaneous operation of multiple multi-organ culture units) and pipette-friendly liquid handling for various conventional cell culture experiments, including cell seeding, medium change, live/dead staining, cell growth analysis, gene expression analysis of collected cells, and liquid chromatography-mass spectrometry analysis of chemical compounds in the culture medium...
December 19, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/29141507/sandwiched-white-adipose-tissue-a-novel-microphysiological-system-of-human-adipose-tissue
#8
Frank H Lau, Kelly Vogel, John P Luckett, Maxwell Hunt, Alicia Meyer, Camille L Rogers, Oren Tessler, Charles L Dupin, Hugo St Hilaire, Kazi N Islam, Trivia Frazier, Jeffrey Gimble, Steven Scahill
White adipose tissue (WAT) is a critical organ in both health and disease. However, physiologically faithful tissue culture models of primary human WAT remain limited, at best. Here we describe a novel WAT culture system in which primary human WAT is sandwiched between tissue-engineered sheets of adipose-derived stromal cells. This construct, called "sandwiched white adipose tissue" (SWAT), can be defined as a Microphysiological System (MPS) since it is a tissue-engineered, multicellular, 3D organ construct produced using human cells...
November 16, 2017: Tissue Engineering. Part C, Methods
https://www.readbyqxmd.com/read/29137633/bi-directional-exosome-driven-intercommunication-between-the-hepatic-niche-and-cancer-cells
#9
Nikolina Dioufa, Amanda M Clark, Bo Ma, Colin H Beckwitt, Alan Wells
BACKGROUND: Our understanding of the multiple roles exosomes play during tumor progression is still very poor and the contribution of the normal tissue derived exosomes in distant seeding and tumor outgrowth has also not been widely appreciated. METHODS: Using our all-human liver microphysiological system (MPS) platform as a model to closely recapitulate the early metastatic events, we isolated exosomes from both tumor cells and liver microenvironment. RESULTS: We observed that while priming of the hepatic niche (HepN) with MDA-231 breast cancer derived exosomes facilitated seeding of the cancer cells in the liver, subsequent tumor outgrowth was diminished; this was consistent with increased entry into dormancy...
November 14, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/29128921/a-microfluidic-in-line-elisa-for-measuring-secreted-protein-under-perfusion
#10
Qiyue Luan, Stacey Cahoon, Agnes Wu, Shyam Sundhar Bale, Martin Yarmush, Abhinav Bhushan
Recent progress in the development of microfluidic microphysiological systems such as 'organs-on-chips' and microfabricated cell culture is geared to simulate organ-level physiology. These tissue models leverage microengineering technologies that provide capabilities of presenting cultured cells with input signals in a more physiologically relevant context such as perfused flow. Proteins that are secreted from cells have important information about the health of the cells. Techniques to quantify cellular proteins include mass spectrometry to ELISA (enzyme-linked immunosorbent assay)...
November 11, 2017: Biomedical Microdevices
https://www.readbyqxmd.com/read/29121458/placental-drug-transport-on-a-chip-a-microengineered-in-vitro-model-of-transporter-mediated-drug-efflux-in-the-human-placental-barrier
#11
Cassidy Blundell, Yoon-Suk Yi, Lin Ma, Emily R Tess, Megan J Farrell, Andrei Georgescu, Lauren M Aleksunes, Dongeun Huh
The current lack of knowledge about the effect of maternally administered drugs on the developing fetus is a major public health concern worldwide. The first critical step toward predicting the safety of medications in pregnancy is to screen drug compounds for their ability to cross the placenta. However, this type of preclinical study has been hampered by the limited capacity of existing in vitro and ex vivo models to mimic physiological drug transport across the maternal-fetal interface in the human placenta...
November 9, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/29065799/fitting-tissue-chips-and-microphysiological-systems-into-the-grand-scheme-of-medicine-biology-pharmacology-and-toxicology
#12
David E Watson, Rosemarie Hunziker, John P Wikswo
Microphysiological systems (MPS), which include engineered organoids (EOs), single organ/tissue chips (TCs), and multiple organs interconnected to create miniature in vitro models of human physiological systems, are rapidly becoming effective tools for drug development and the mechanistic understanding of tissue physiology and pathophysiology. The second MPS thematic issue of Experimental Biology and Medicine comprises 15 articles by scientists and engineers from the National Institutes of Health, the IQ Consortium, the Food and Drug Administration, and Environmental Protection Agency, an MPS company, and academia...
October 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29065798/microphysiologic-systems-in-female-reproductive-biology
#13
REVIEW
Alexandria N Young, Georgette Moyle-Heyrman, J Julie Kim, Joanna E Burdette
Microphysiologic systems (MPS), including new organ-on-a-chip technologies, recapitulate tissue microenvironments by employing specially designed tissue or cell culturing techniques and microfluidic flow. Such systems are designed to incorporate physiologic factors that conventional 2D or even 3D systems cannot, such as the multicellular dynamics of a tissue-tissue interface or physical forces like fluid sheer stress. The female reproductive system is a series of interconnected organs that are necessary to produce eggs, support embryo development and female health, and impact the functioning of non-reproductive tissues throughout the body...
November 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29065797/self-contained-low-cost-body-on-a-chip-systems-for-drug-development
#14
REVIEW
Ying I Wang, Carlota Oleaga, Christopher J Long, Mandy B Esch, Christopher W McAleer, Paula G Miller, James J Hickman, Michael L Shuler
Integrated multi-organ microphysiological systems are an evolving tool for preclinical evaluation of the potential toxicity and efficacy of drug candidates. Such systems, also known as Body-on-a-Chip devices, have a great potential to increase the successful conversion of drug candidates entering clinical trials into approved drugs. Systems, to be attractive for commercial adoption, need to be inexpensive, easy to operate, and give reproducible results. Further, the ability to measure functional responses, such as electrical activity, force generation, and barrier integrity of organ surrogates, enhances the ability to monitor response to drugs...
November 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29065796/circadian-hormone-control-in-a-human-on-a-chip-in-vitro-biology-s-ignored-component
#15
REVIEW
Kevin J Cyr, Omero M Avaldi, John P Wikswo
Organs-on-Chips (OoCs) are poised to reshape dramatically the study of biology by replicating in vivo the function of individual and coupled human organs. Such microphysiological systems (MPS) have already recreated complex physiological responses necessary to simulate human organ function not evident in two-dimensional in vitro biological experiments. OoC researchers hope to streamline pharmaceutical development, accelerate toxicology studies, limit animal testing, and provide new insights beyond the capability of current biological models...
November 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29058990/introduction-to-the-theme-new-approaches-for-studying-drug-and-toxicant-action-applications-to-drug-discovery-and-development
#16
Paul A Insel, Susan G Amara, Terrence F Blaschke, Urs A Meyer
The theme "New Approaches for Studying Drug and Toxicant Action: Applications to Drug Discovery and Development" links 13 articles in this volume of the Annual Review of Pharmacology and Toxicology (ARPT). The engaging prefatory articles by Arthur Cho and Robert Lefkowitz set the stage for this theme and for the reviews that insightfully describe new approaches that advance research and discovery in pharmacology and toxicology. Examples include the progress being made in developing Organson- Chips/microphysiological systems and human induced pluripotent stem cell (iPSC)-derived cells to aid in understanding cell and tissue pharmacokinetics, action, and toxicity; the recognition of the importance of circadian rhythm, the microbiome, and epigenetics in drug and toxicant responses; and the application of results from new types of patient-derived information to create personalized/precision medicine, including therapeutics for pain, which may perhaps provide help in dealing with the opioid epidemic in the United States...
October 20, 2017: Annual Review of Pharmacology and Toxicology
https://www.readbyqxmd.com/read/29029591/application-of-microphysiological-systems-to-enhance-safety-assessment-in-drug-discovery
#17
Lorna Ewart, Eva-Maria Dehne, Kristin Fabre, Susan Gibbs, James Hickman, Ellinor Hornberg, Magnus Ingelman-Sundberg, Kyung-Jin Jang, David R Jones, Volker M Lauschke, Uwe Marx, Jerome T Mettetal, Amy Pointon, Dominic Williams, Wolfram-Hubertus Zimmermann, Peter Newham
Enhancing the early detection of new therapies that are likely to carry a safety liability in the context of the intended patient population would provide a major advance in drug discovery. Microphysiological systems (MPS) technology offers an opportunity to support enhanced preclinical to clinical translation through the generation of higher-quality preclinical physiological data. In this review, we highlight this technological opportunity by focusing on key target organs associated with drug safety and metabolism...
October 13, 2017: Annual Review of Pharmacology and Toxicology
https://www.readbyqxmd.com/read/28985032/organ-on-a-chip-systems-for-women-s-health-applications
#18
REVIEW
Janna Nawroth, Julia Rogal, Martin Weiss, Sara Y Brucker, Peter Loskill
Biomedical research, for a long time, has paid little attention to the influence of sex in many areas of study, ranging from molecular and cellular biology to animal models and clinical studies on human subjects. Many studies solely rely on male cells/tissues/animals/humans, although there are profound differences in male and female physiology, which can significantly impact disease mechanisms, toxicity of compounds, and efficacy of pharmaceuticals. In vitro systems have been traditionally very limited in their capacity to recapitulate female-specific physiology and anatomy such as dynamic sex-hormone levels and the complex interdependencies of female reproductive tract organs...
October 6, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28976521/cardiac-microphysiological-devices-with-flexible-thin-film-sensors-for-higher-throughput-drug-screening
#19
Johan U Lind, Moran Yadid, Ian Perkins, Blakely B O'Connor, Feyisayo Eweje, Christophe O Chantre, Matthew A Hemphill, Hongyan Yuan, Patrick H Campbell, Joost J Vlassak, Kevin K Parker
Microphysiological systems and organs-on-chips promise to accelerate biomedical and pharmaceutical research by providing accurate in vitro replicas of human tissue. Aside from addressing the physiological accuracy of the model tissues, there is a pressing need for improving the throughput of these platforms. To do so, scalable data acquisition strategies must be introduced. To this end, we here present an instrumented 24-well plate platform for higher-throughput studies of engineered human stem cell-derived cardiac muscle tissues that recapitulate the laminar structure of the native ventricle...
October 25, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/28884006/engineering-challenges-in-microphysiological-systems
#20
EDITORIAL
Yu Shrike Zhang
No abstract text is available yet for this article.
August 2017: Future Science OA
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