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https://www.readbyqxmd.com/read/28092941/21st-century-cell-culture-for-21st-century-toxicology
#1
David Pamies, Thomas Hartung
There is no good science in bad models. Cell culture is especially prone to artifacts. A number of novel cell culture technologies have become more broadly available in the 21st century, which allow overcoming limitations of traditional culture and are more physiologically relevant. These include the use of stem-cell derived human cells, cocultures of different cell types, scaffolds and extracellular matrices, perfusion platforms (such as microfluidics), 3D culture, organ-on-chip technologies, tissue architecture, and organ functionality...
January 17, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28092382/a-vascularized-and-perfused-organ-on-a-chip-platform-for-large-scale-drug-screening-applications
#2
Duc T T Phan, Xiaolin Wang, Brianna M Craver, Agua Sobrino, Da Zhao, Jerry C Chen, Lilian Y N Lee, Steven C George, Abraham P Lee, Christopher C W Hughes
There is a growing awareness that complex 3-dimensional (3D) organs are not well represented by monolayers of a single cell type - the standard format for many drug screens. To address this deficiency, and with the goal of improving screens so that drugs with good efficacy and low toxicity can be identified, microphysiological systems (MPS) are being developed that better capture the complexity of in vivo physiology. We have previously described an organ-on-a-chip platform that incorporates perfused microvessels, such that survival of the surrounding tissue is entirely dependent on delivery of nutrients through the vessels...
January 16, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/28089783/characterization-of-rat-or-human-hepatocytes-cultured-in-microphysiological-systems-mps-to-identify-hepatotoxicity
#3
Shih-Yu Chang, Jenna L Voellinger, Kirk P Van Ness, Brian Chapron, Rachel M Shaffer, Thomas Neumann, Collin C White, Terrance J Kavanagh, Edward J Kelly, David L Eaton
The liver is the main site for drug and xenobiotics metabolism, including inactivation or bioactivation. In order to improve the predictability of drug safety and efficacy in clinical development, and to facilitate the evaluation of the potential human health effects from exposure to environmental contaminants, there is a critical need to accurately model human organ systems such as the liver in vitro. We are developing a microphysiological system (MPS) based on a new commercial microfluidic platform (Nortis, Inc...
January 12, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28078768/microphysiological-systems-organs-on-chips-for-drug-efficacy-and-toxicity-testing
#4
Lucie A Low, Danilo A Tagle
No abstract text is available yet for this article.
January 11, 2017: Clinical and Translational Science
https://www.readbyqxmd.com/read/27990124/endothelial-progenitor-cells-physiology-and-metabolic-plasticity-in-brain-angiogenesis-and-blood-brain-barrier-modeling
#5
REVIEW
Natalia A Malinovskaya, Yulia K Komleva, Vladimir V Salmin, Andrey V Morgun, Anton N Shuvaev, Yulia A Panina, Elizaveta B Boitsova, Alla B Salmina
Currently, there is a considerable interest to the assessment of blood-brain barrier (BBB) development as a part of cerebral angiogenesis developmental program. Embryonic and adult angiogenesis in the brain is governed by the coordinated activity of endothelial progenitor cells, brain microvascular endothelial cells, and non-endothelial cells contributing to the establishment of the BBB (pericytes, astrocytes, neurons). Metabolic and functional plasticity of endothelial progenitor cells controls their timely recruitment, precise homing to the brain microvessels, and efficient support of brain angiogenesis...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27910972/a-liver-microphysiological-system-of-tumor-cell-dormancy-and-inflammatory-responsiveness-is-affected-by-scaffold-properties
#6
A M Clark, S E Wheeler, C L Young, L Stockdale, J Shepard Neiman, W Zhao, D B Stolz, R Venkataramanan, D Lauffenburger, L Griffith, A Wells
Distant metastasis is the major cause of breast cancer-related mortality, commonly emerging clinically after 5 or more years of seeming 'cure' of the primary tumor, indicating a quiescent dormancy. The lack of relevant accessible model systems for metastasis that recreate this latent stage has hindered our understanding of the molecular basis and the development of therapies against these lethal outgrowths. We previously reported on the development of an all-human 3D ex vivo hepatic microphysiological system that reproduces several features of liver physiology and enables spontaneous dormancy in a subpopulation of breast cancer cells...
December 20, 2016: Lab on a Chip
https://www.readbyqxmd.com/read/27904714/facilitating-the-commercialization-and-use-of-organ-platforms-generated-by-the-microphysiological-systems-tissue-chip-program-through-public-private-partnerships
#7
REVIEW
Christine A Livingston, Kristin M Fabre, Danilo A Tagle
Microphysiological systems (organs-on-chips, tissue chips) are devices designed to recapitulate human physiology that could be used to better understand drug responses not easily addressed using other in vivo systems or in vitro animal models. Although still in development, initial results seem promising as tissue chips exhibit in vivo systems-like functional responses. The National Center for Advancing Translation Science (NCATS) identifies this technology as a potential tool that could improve the process of getting safer, more effective treatments to patients, and has led to the Tissue Chip Program, which aims to develop, integrate and validate major organ systems for testing...
2016: Computational and Structural Biotechnology Journal
https://www.readbyqxmd.com/read/27883356/a-human-brain-microphysiological-system-derived-from-induced-pluripotent-stem-cells-to-study-neurological-diseases-and-toxicity
#8
David Pamies, Paula Barreras, Katharina Block, Georgia Makri, Anupama Kumar, Daphne Wiersma, Lenna Smirnova, Ce Zhang, Joseph Bressler, Kimberly M Christian, Georgina Harris, Guo-Li Ming, Cindy J Berlinicke, Kelly Kyro, Hongjun Song, Carlos A Pardo, Thomas Hartung, Helena T Hogberg
Human in-vitro models of brain neurophysiology are needed to investigate molecular and cellular mechanisms associated with neurological disorders and neurotoxicity. We have developed a reproducible iPSC-derived human 3D brain microphysiological system (BMPS), comprised of differentiated mature neurons and glial cells (astrocytes and oligodendrocytes) that reproduce neuronal-glial interactions and connectivity. BMPS mature over eight weeks and show the critical elements of neuronal function: synaptogenesis and neuron-to-neuron (e...
November 24, 2016: ALTEX
https://www.readbyqxmd.com/read/27775708/instrumented-cardiac-microphysiological-devices-via-multimaterial-three-dimensional-printing
#9
Johan U Lind, Travis A Busbee, Alexander D Valentine, Francesco S Pasqualini, Hongyan Yuan, Moran Yadid, Sung-Jin Park, Arda Kotikian, Alexander P Nesmith, Patrick H Campbell, Joost J Vlassak, Jennifer A Lewis, Kevin K Parker
Biomedical research has relied on animal studies and conventional cell cultures for decades. Recently, microphysiological systems (MPS), also known as organs-on-chips, that recapitulate the structure and function of native tissues in vitro, have emerged as a promising alternative. However, current MPS typically lack integrated sensors and their fabrication requires multi-step lithographic processes. Here, we introduce a facile route for fabricating a new class of instrumented cardiac microphysiological devices via multimaterial three-dimensional (3D) printing...
October 24, 2016: Nature Materials
https://www.readbyqxmd.com/read/27768243/prenatal-exposure-to-environmental-factors-and-congenital-limb-defects
#10
Peter G Alexander, Karen L Clark, Rocky S Tuan
Limb congenital defects afflict approximately 0.6:1000 live births. In addition to genetic factors, prenatal exposure to drugs and environmental toxicants, represents a major contributing factor to limb defects. Examples of well-recognized limb teratogenic agents include thalidomide, warfarin, valproic acid, misoprostol, and phenytoin. While the mechanism by which these agents cause dymorphogenesis is increasingly clear, prediction of the limb teratogenicity of many thousands of as yet uncharacterized environmental factors (pollutants) remains inexact...
October 21, 2016: Birth Defects Research. Part C, Embryo Today: Reviews
https://www.readbyqxmd.com/read/27760784/quantitative-assessment-of-population-variability-in-hepatic-drug-metabolism-using-a-perfused-three-dimensional-human-liver-microphysiological-system
#11
N Tsamandouras, T Kostrzewski, C L Stokes, L G Griffith, D J Hughes, M Cirit
In this work, we first describe the population variability in hepatic drug metabolism using cryopreserved hepatocytes from five different donors cultured in a perfused three-dimensional human liver microphysiological system, and then show how the resulting data can be integrated with a modeling and simulation framework to accomplish in vitro-in vivo translation. For each donor, metabolic depletion profiles of six compounds (phenacetin, diclofenac, lidocaine, ibuprofen, propranolol, and prednisolone) were measured, along with metabolite formation, mRNA levels of 90 metabolism-related genes, and markers of functional viability [lactate dehydrogenase (LDH) release, albumin, and urea production]...
January 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/27563856/cover-image-volume-113-number-10-october-2016
#12
Paula G Miller, Michael L Shuler
Cover Legend The design and operation of a bidirectional flow, pumpless 14 chamber system representing 13 tissues/organs with both barrier and nonbarrier tissue chambers is described. Viability across all compartments was initially demonstrated with one cell line. Then viability and functionality in the device was retained for 7 days using 5 representative cell lines and compared to static controls. The cover image, by Michael L. Shuler and Paula G. Miller, is based on the Article Design and demonstration of a pumpless 14 compartment microphysiological system, DOI: 10...
October 2016: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/27560793/the-intercell-dynamics-of-t-cells-and-dendritic-cells-in-a-lymph-node-on-a-chip-flow-device
#13
Patrícia Moura Rosa, Nimi Gopalakrishnan, Hany Ibrahim, Markus Haug, Øyvind Halaas
T cells play a central role in immunity towards cancer and infectious diseases. T cell responses are initiated in the T cell zone of the lymph node (LN), where resident antigen-bearing dendritic cells (DCs) prime and activate antigen-specific T cells passing by. In the present study, we investigated the T cell : DC interaction in a microfluidic device to understand the intercellular dynamics and physiological conditions in the LN. We show random migration of antigen-specific T cells onto the antigen-presenting DC monolayer independent of the flow direction with a mean T cell : DC dwell time of 12...
October 7, 2016: Lab on a Chip
https://www.readbyqxmd.com/read/27549930/3d-microtumors-in-vitro-supported-by-perfused-vascular-networks
#14
Agua Sobrino, Duc T T Phan, Rupsa Datta, Xiaolin Wang, Stephanie J Hachey, Mónica Romero-López, Enrico Gratton, Abraham P Lee, Steven C George, Christopher C W Hughes
There is a growing interest in developing microphysiological systems that can be used to model both normal and pathological human organs in vitro. This "organs-on-chips" approach aims to capture key structural and physiological characteristics of the target tissue. Here we describe in vitro vascularized microtumors (VMTs). This "tumor-on-a-chip" platform incorporates human tumor and stromal cells that grow in a 3D extracellular matrix and that depend for survival on nutrient delivery through living, perfused microvessels...
August 23, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27521113/development-of-a-microphysiological-model-of-human-kidney-proximal-tubule-function
#15
Elijah J Weber, Alenka Chapron, Brian D Chapron, Jenna L Voellinger, Kevin A Lidberg, Catherine K Yeung, Zhican Wang, Yoshiyuki Yamaura, Dale W Hailey, Thomas Neumann, Danny D Shen, Kenneth E Thummel, Kimberly A Muczynski, Jonathan Himmelfarb, Edward J Kelly
The kidney proximal tubule is the primary site in the nephron for excretion of waste products through a combination of active uptake and secretory processes and is also a primary target of drug-induced nephrotoxicity. Here, we describe the development and functional characterization of a 3-dimensional flow-directed human kidney proximal tubule microphysiological system. The system replicates the polarity of the proximal tubule, expresses appropriate marker proteins, exhibits biochemical and synthetic activities, as well as secretory and reabsorptive processes associated with proximal tubule function in vivo...
September 2016: Kidney International
https://www.readbyqxmd.com/read/27448090/liver-and-kidney-on-chips-microphysiological-models-to-understand-transporter-function
#16
S Y Chang, E J Weber, Kp Van Ness, D L Eaton, E J Kelly
Because of complex cellular microenvironments of both the liver and kidneys, accurate modeling of transport function has remained a challenge, leaving a dire need for models that can faithfully recapitulate both the architecture and cell-cell interactions observed in vivo. The study of hepatic and renal transport function is a fundamental component of understanding the metabolic fate of drugs and xenobiotics; however, there are few in vitro systems conducive for these types of studies. For both the hepatic and renal systems, we provide an overview of the location and function of the most significant phase I/II/III (transporter) of enzymes, and then review current in vitro systems for the suitability of a transporter function study and provide details on microphysiological systems that lead the field in these investigations...
November 2016: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/27390264/liver-metastases-microenvironments-and-ex-vivo-models
#17
Amanda M Clark, Bo Ma, D Lansing Taylor, Linda Griffith, Alan Wells
The liver is a highly metastasis-permissive organ, tumor seeding of which usually portends mortality. Its unique and diverse architectural and cellular composition enable the liver to undertake numerous specialized functions, however, this distinctive biology, notably its hemodynamic features and unique microenvironment, renders the liver intrinsically hospitable to disseminated tumor cells. The particular focus for this perspective is the bidirectional interactions between the disseminated tumor cells and the unique resident cell populations of the liver; notably, parenchymal hepatocytes and non-parenchymal liver sinusoidal endothelial, Kupffer, and hepatic stellate cells...
September 2016: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/27303643/advancing-cardiovascular-tissue-engineering
#18
REVIEW
George A Truskey
Cardiovascular tissue engineering offers the promise of biologically based repair of injured and damaged blood vessels, valves, and cardiac tissue. Major advances in cardiovascular tissue engineering over the past few years involve improved methods to promote the establishment and differentiation of induced pluripotent stem cells (iPSCs), scaffolds from decellularized tissue that may produce more highly differentiated tissues and advance clinical translation, improved methods to promote vascularization, and novel in vitro microphysiological systems to model normal and diseased tissue function...
2016: F1000Research
https://www.readbyqxmd.com/read/27291426/human-gut-on-a-chip-technology-will-this-revolutionize-our-understanding-of-ibd-and-future-treatments
#19
Jaewon Lee, Jin-Ha Choi, Hyun Jung Kim
No abstract text is available yet for this article.
August 2016: Expert Review of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/27229450/a-microphysiological-model-of-the-human-placental-barrier
#20
Cassidy Blundell, Emily R Tess, Ariana S R Schanzer, Christos Coutifaris, Emily J Su, Samuel Parry, Dongeun Huh
During human pregnancy, the fetal circulation is separated from maternal blood in the placenta by two cell layers - the fetal capillary endothelium and placental trophoblast. This placental barrier plays an essential role in fetal development and health by tightly regulating the exchange of endogenous and exogenous materials between the mother and the fetus. Here we present a microengineered device that provides a novel platform to mimic the structural and functional complexity of this specialized tissue in vitro...
August 2, 2016: Lab on a Chip
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