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Microphysiological system

Collin D Edington, Wen Li Kelly Chen, Emily Geishecker, Timothy Kassis, Luis R Soenksen, Brij M Bhushan, Duncan Freake, Jared Kirschner, Christian Maass, Nikolaos Tsamandouras, Jorge Valdez, Christi D Cook, Tom Parent, Stephen Snyder, Jiajie Yu, Emily Suter, Michael Shockley, Jason Velazquez, Jeremy J Velazquez, Linda Stockdale, Julia P Papps, Iris Lee, Nicholas Vann, Mario Gamboa, Matthew E LaBarge, Zhe Zhong, Xin Wang, Laurie A Boyer, Douglas A Lauffenburger, Rebecca L Carrier, Catherine Communal, Steven R Tannenbaum, Cynthia L Stokes, David J Hughes, Gaurav Rohatgi, David L Trumper, Murat Cirit, Linda G Griffith
Microphysiological systems (MPSs) are in vitro models that capture facets of in vivo organ function through use of specialized culture microenvironments, including 3D matrices and microperfusion. Here, we report an approach to co-culture multiple different MPSs linked together physiologically on re-useable, open-system microfluidic platforms that are compatible with the quantitative study of a range of compounds, including lipophilic drugs. We describe three different platform designs - "4-way", "7-way", and "10-way" - each accommodating a mixing chamber and up to 4, 7, or 10 MPSs...
March 14, 2018: Scientific Reports
Yasuyuki Sakai, Marie Shinohara
Animal-free and mechanism-based understanding of human body responses is the ultimate goal of alternative to animal experiments. To achieve this goal, integration of advanced cell-based assays using iPS/ES cell technologies with various numerical methods are required. In this review, from the standpoint of tissue engineering, we focused first on the enhancement of physiological relevance of tissue culture models by overcoming the problem between 3D cellular organization and oxygen/nutrient supply. Second, we summarized the concept and actual systems of microfluidic-based body/organ on-a-chip systems, also called as microphysiological system, MPS, particularly for liver on-a-chip systems...
2018: Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica
Na N Guan, Nimish Sharma, Katarina Hallén-Grufman, Edwin W H Jager, Karl Svennersten
The capacity to store urine and initiate voiding is a valued characteristic of the human urinary bladder. To maintain this feature, it is necessary that the bladder can sense when it is full and when it is time to void. The bladder has a specialized epithelium called urothelium that is believed to be important for its sensory function. It has been suggested that autocrine ATP signalling contributes to this sensory function of the urothelium. There is well-established evidence that ATP is released via vesicular exocytosis as well as by pannexin hemichannels upon mechanical stimulation...
February 1, 2018: Journal of Cellular and Molecular Medicine
Mario M Modena, Ketki Chawla, Patrick M Misun, Andreas Hierlemann
Technological advances in microfabrication techniques in combination with organotypic cell and tissue models have enabled the realization of microphysiological systems capable of recapitulating aspects of human physiology in vitro with great fidelity. Concurrently, a number of analysis techniques has been developed to probe and characterize these model systems. However, many assays are still performed off-line, which severely compromises the possibility to obtain real-time information from the samples under examination, and which also limits the use of these platforms in high-throughput analysis...
January 30, 2018: ACS Chemical Biology
Amanda M Clark, Manu Kumar, Sarah Wheeler, Carissa Young, Raman Venkataramanan, Donna Stolz, Linda Griffith, Douglas A Lauffenburger, Alan Wells
Breast cancer mortality predominantly results from dormant micrometastases that emerge as fatal outgrowths years after initial diagnosis. In order to gain insights concerning factors associated with emergence of liver metastases, we recreated spontaneous dormancy in an all-human ex vivo hepatic microphysiological system (MPS). Seeding this MPS with small numbers (<0.05% by cell count) of the aggressive MDA-MB-231 breast cancer cell line, two populations formed: actively proliferating ('growing'; EdU+), and spontaneously quiescent ('dormant'; EdU-)...
January 20, 2018: Molecular & Cellular Proteomics: MCP
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
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
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...
February 2018: Drug Metabolism and Pharmacokinetics
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
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...
January 2018: Advanced Healthcare Materials
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
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
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
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
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
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
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
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
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
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
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