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Microphysiological system

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https://www.readbyqxmd.com/read/28670478/tailoring-cardiac-environment-in-microphysiological-systems-an-outlook-on-current-and-perspective-heart-on-chip-platforms
#1
EDITORIAL
Giovanni Stefano Ugolini, Roberta Visone, Daniela Cruz-Moreira, Alberto Redaelli, Marco Rasponi
No abstract text is available yet for this article.
June 2017: Future Science OA
https://www.readbyqxmd.com/read/28670475/the-ascendance-of-microphysiological-systems-to-solve-the-drug-testing-dilemma
#2
REVIEW
Eva-Maria Dehne, Tobias Hasenberg, Uwe Marx
The development of drugs is a process obstructed with manifold security and efficacy concerns. Although animal models are still widely used to meet the diligence required, they are regarded as outdated tools with limited predictability. Novel microphysiological systems intend to create systemic models of human biology. Their ability to host 3D organoid constructs in a controlled microenvironment with mechanical and electrophysiological stimuli enables them to create and maintain homeostasis. These platforms are, thus, envisioned to be superior tools for testing and developing substances such as drugs, cosmetics and chemicals...
June 2017: Future Science OA
https://www.readbyqxmd.com/read/28667746/integrated-gut-liver-microphysiological-systems-elucidates-inflammatory-inter-tissue-crosstalk
#3
Wen Li Kelly Chen, Collin Edington, Emily Suter, Jiajie Yu, Jeremy J Velazquez, Jason G Velazquez, Michael Shockley, Emma M Large, Raman Venkataramanan, David J Hughes, Cynthia L Stokes, David L Trumper, Rebecca L Carrier, Murat Cirit, Linda G Griffith, Douglas A Lauffenburger
A capability for analyzing complex cellular communication among tissues is important in drug discovery and development, and in vitro technologies for doing so are required for human applications. A prominent instance is communication between the gut and the liver, whereby perturbations of one tissue can influence behavior of the other. Here, we present a study on human gut-liver tissue interactions under normal and inflammatory contexts, via an integrative multi-organ platform comprising human liver (hepatocytes and Kupffer cells) and intestinal (enterocyte, goblet cells, and dendritic cells) models...
July 1, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28658972/programming-microphysiological-systems-for-children-s-health-protection
#4
T B Knudsen, B Klieforth, W Slikker
Microphysiological systems (MPS) and computer simulation models that recapitulate the underlying biology and toxicology of critical developmental transitions are emerging tools for developmental effects assessment of drugs/chemicals. Opportunities and challenges exist for their application to alternative, more public health relevant and efficient chemical toxicity testing methods. This is especially pertinent to children's health research and the evaluation of complex embryological and reproductive impacts of drug/chemical exposure...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28622076/human-ips-derived-endothelial-cells-for-3d-microphysiological-systems
#5
Yosuke K Kurokawa, Rose T Yin, Michael R Shang, Venktesh S Shirure, Monica L Moya, Steven C George
Microphysiological systems, or "organ-on-a-chip", platforms, aim to recapitulate in vivo physiology using small-scale in vitro tissue models of human physiology. While significant efforts have been made to create vascularized tissues, most reports utilize primary endothelial cells which hinder reproducibility. Here we report the use of human induced pluripotent stem cell-derived endothelial cells (iPS-EC) in developing 3D microvascular networks. We established a CDH5-mCherry reporter iPS cell line, which expresses the vascular endothelial (VE)-cadherin fused to mCherry...
June 16, 2017: Tissue Engineering. Part C, Methods
https://www.readbyqxmd.com/read/28534432/gastrointestinal-microphysiological-systems
#6
Sarah E Blutt, James R Broughman, Winnie Zou, Xi-Lei Zeng, Umesh C Karandikar, Julie In, Nicholas C Zachos, Olga Kovbasnjuk, Mark Donowitz, Mary K Estes
Gastrointestinal diseases are a significant health care and economic burden. Prevention and treatment of these diseases have been limited by the available human biologic models. Microphysiological systems comprise organ-specific human cultures that recapitulate many structural, biological, and functional properties of the organ in smaller scale including aspects of flow, shear stress and chemical gradients. The development of intestinal microphysiological system platforms represents a critical component in improving our understanding, prevention, and treatment of gastrointestinal diseases...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28533121/recent-progress-in-hepatocyte-culture-models-and-their-application-to-the-assessment-of-drug-metabolism-transport-and-toxicity-in-drug-discovery-the-value-of-tissue-engineering-for-the-successful-development-of-a-microphysiological-system
#7
REVIEW
Kazuhiro Tetsuka, Masato Ohbuchi, Kenji Tabata
Tissue engineering technology has provided many useful culture models. This article reviews the merits of this technology in a hepatocyte culture system, and describes the applications of the sandwich-cultured hepatocyte model in drug discovery. In addition, we also review recent investigations of the utility of the three-dimensional bioprinted human liver tissue model and spheroid model. Finally, we present the future direction and developmental challenges of a hepatocyte culture model for the successful establishment of a microphysiological system, represented as an organ-on-a-chip and even as a human-on-a-chip...
May 19, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28504617/opportunities-and-challenges-in-the-wider-adoption-of-liver-and-interconnected-microphysiological-systems
#8
David J Hughes, Tomasz Kostrzewski, Emma L Sceats
Liver disease represents a growing global health burden. The development of in vitro liver models which allow the study of disease and the prediction of metabolism and drug-induced liver injury in humans remains a challenge. The maintenance of functional primary hepatocytes cultures, the parenchymal cell of the liver, has historically been difficult with dedifferentiation and the consequent loss of hepatic function limiting utility. The desire for longer term functional liver cultures sparked the development of numerous systems, including collagen sandwiches, spheroids, micropatterned co-cultures and liver microphysiological systems...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28488235/emulating-host-microbiome-ecosystem-of-human-gastrointestinal-tract-in-vitro
#9
Gun-Seok Park, Min Hee Park, Woojung Shin, Connie Zhao, Sameer Sheikh, So Jung Oh, Hyun Jung Kim
The human gut microbiome performs prodigious physiological functions such as production of microbial metabolites, modulation of nutrient digestion and drug metabolism, control of immune system, and prevention of infection. Paradoxically, gut microbiome can also negatively orchestrate the host responses in diseases or chronic disorders, suggesting that the regulated and balanced host-gut microbiome crosstalk is a salient prerequisite in gastrointestinal physiology. To understand the pathophysiological role of host-microbiome crosstalk, it is critical to recreate in vivo relevant models of the host-gut microbiome ecosystem in human...
May 10, 2017: Stem Cell Reviews
https://www.readbyqxmd.com/read/28488234/microphysiological-human-brain-and-neural-systems-on-a-chip-potential-alternatives-to-small-animal-models-and-emerging-platforms-for-drug-discovery-and-personalized-medicine
#10
Alexander P Haring, Harald Sontheimer, Blake N Johnson
Translational challenges associated with reductionist modeling approaches, as well as ethical concerns and economic implications of small animal testing, drive the need for developing microphysiological neural systems for modeling human neurological diseases, disorders, and injuries. Here, we provide a comprehensive review of microphysiological brain and neural systems-on-a-chip (NSCs) for modeling higher order trajectories in the human nervous system. Societal, economic, and national security impacts of neurological diseases, disorders, and injuries are highlighted to identify critical NSC application spaces...
May 10, 2017: Stem Cell Reviews
https://www.readbyqxmd.com/read/28467181/pre-clinical-and-clinical-investigations-of-metabolic-zonation-in-liver-diseases-the-potential-of-microphysiology-systems
#11
Alejandro Soto-Gutierrez, Albert Gough, Lawrence A Vernetti, D L Taylor, Satdarshan P Monga
The establishment of metabolic zonation within a hepatic lobule ascribes specific functions to hepatocytes based on unique, location-dependent gene expression patterns. Recently, there have been significant developments in the field of metabolic liver zonation. A little over a decade ago, the role of β-catenin signaling was identified as a key regulator of gene expression and function in pericentral hepatocytes. Since then, additional molecules have been identified that regulate the pattern of Wnt/β-catenin signaling within a lobule and determine gene expression and function in other hepatic zones...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28450578/integrated-assessment-of-diclofenac-biotransformation-pharmacokinetics-and-omics-based-toxicity-in-a-three-dimensional-human-liver-immunocompetent-coculture-system
#12
Ujjal Sarkar, Kodihalli C Ravindra, Emma Large, Carissa L Young, Dinelia Rivera-Burgos, Jiajie Yu, Murat Cirit, David J Hughes, John S Wishnok, Douglas A Lauffenburger, Linda G Griffith, Steven R Tannenbaum
In vitro hepatocyte culture systems have inherent limitations in capturing known human drug toxicities that arise from complex immune responses. Therefore, we established and characterized a liver immunocompetent coculture model and evaluated diclofenac (DCF) metabolic profiles, in vitro-in vivo clearance correlations, toxicological responses, and acute phase responses using liquid chromatography-tandem mass spectrometry. DCF biotransformation was assessed after 48 hours of culture, and the major phase I and II metabolites were similar to the in vivo DCF metabolism profile in humans...
July 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28445465/assembly-of-functionally-integrated-human-forebrain-spheroids
#13
Fikri Birey, Jimena Andersen, Christopher D Makinson, Saiful Islam, Wu Wei, Nina Huber, H Christina Fan, Kimberly R Cordes Metzler, Georgia Panagiotakos, Nicholas Thom, Nancy A O'Rourke, Lars M Steinmetz, Jonathan A Bernstein, Joachim Hallmayer, John R Huguenard, Sergiu P Paşca
The development of the nervous system involves a coordinated succession of events including the migration of GABAergic (γ-aminobutyric-acid-releasing) neurons from ventral to dorsal forebrain and their integration into cortical circuits. However, these interregional interactions have not yet been modelled with human cells. Here we generate three-dimensional spheroids from human pluripotent stem cells that resemble either the dorsal or ventral forebrain and contain cortical glutamatergic or GABAergic neurons...
May 4, 2017: Nature
https://www.readbyqxmd.com/read/28425064/a-pathway-to-personalizing-therapy-for-metastases-using-liver-on-a-chip-platforms
#14
A S Khazali, A M Clark, A Wells
Metastasis accounts for most cancer-related deaths. The majority of solid cancers, including those of the breast, colorectum, prostate and skin, metastasize at significant levels to the liver due to its hemodynamic as well as tumor permissive microenvironmental properties. As this occurs prior to detection and treatment of the primary tumor, we need to target liver metastases to improve patients' outcomes. Animal models, while proven to be useful in mechanistic studies, do not represent the heterogeneity of human population especially in drug metabolism lack proper human cell-cell interactions, and this gap between animals and humans results in costly and inefficient drug discovery...
June 2017: Stem Cell Reviews
https://www.readbyqxmd.com/read/28409533/control-of-oxygen-tension-recapitulates-zone-specific-functions-in-human-liver-microphysiology-systems
#15
Felipe T Lee-Montiel, Subin M George, Albert H Gough, Anup D Sharma, Juanfang Wu, Richard DeBiasio, Lawrence A Vernetti, D Lansing Taylor
This article describes our next generation human Liver Acinus MicroPhysiology System (LAMPS). The key demonstration of this study was that Zone 1 and Zone 3 microenvironments can be established by controlling the oxygen tension in individual devices over the range of ca. 3 to 13%. The oxygen tension was computationally modeled using input on the microfluidic device dimensions, numbers of cells, oxygen consumption rates of hepatocytes, the diffusion coefficients of oxygen in different materials and the flow rate of media in the MicroPhysiology System (MPS)...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28343437/organs-on-chips-progress-challenges-and-future-directions
#16
Lucie A Low, Danilo A Tagle
The National Institutes of Health Microphysiological Systems (MPS) program, led by the National Center for Advancing Translational Sciences, is part of a joint effort on MPS development with the Defense Advanced Research Projects Agency and with regulatory guidance from FDA, is now in its final year of funding. The program has produced many tangible outcomes in tissue chip development in terms of stem cell differentiation, microfluidic engineering, platform development, and single and multi-organ systems-and continues to help facilitate the acceptance and use of tissue chips by the wider community...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28300206/corrigendum-functional-coupling-of-human-microphysiology-systems-intestine-liver-kidney-proximal-tubule-blood-brain-barrier-and-skeletal-muscle
#17
Lawrence Vernetti, Albert Gough, Nicholas Baetz, Sarah Blutt, James R Broughman, Jacquelyn A Brown, Jennifer Foulke-Abel, Nesrin Hasan, Julie In, Edward Kelly, Olga Kovbasnjuk, Jonathan Repper, Nina Senutovitch, Janet Stabb, Catherine Yeung, Nick C Zachos, Mark Donowitz, Mary Estes, Jonathan Himmelfarb, George Truskey, John P Wikswo, D Lansing Taylor
No abstract text is available yet for this article.
March 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28267162/multi-functional-scaling-methodology-for-translational-pharmacokinetic-and-pharmacodynamic-applications-using-integrated-microphysiological-systems-mps
#18
Christian Maass, Cynthia L Stokes, Linda G Griffith, Murat Cirit
Microphysiological systems (MPS) provide relevant physiological environments in vitro for studies of pharmacokinetics, pharmacodynamics and biological mechanisms for translational research. Designing multi-MPS platforms is essential to study multi-organ systems. Typical design approaches, including direct and allometric scaling, scale each MPS individually and are based on relative sizes not function. This study's aim was to develop a new multi-functional scaling approach for integrated multi-MPS platform design for specific applications...
April 18, 2017: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/28195514/blood-brain-barrier-on-a-chip-microphysiological-systems-that-capture-the-complexity-of-the-blood-central-nervous-system-interface
#19
Duc Tt Phan, R Hugh F Bender, Jillian W Andrejecsk, Agua Sobrino, Stephanie J Hachey, Steven C George, Christopher Cw Hughes
The blood-brain barrier is a dynamic and highly organized structure that strictly regulates the molecules allowed to cross the brain vasculature into the central nervous system. The blood-brain barrier pathology has been associated with a number of central nervous system diseases, including vascular malformations, stroke/vascular dementia, Alzheimer's disease, multiple sclerosis, and various neurological tumors including glioblastoma multiforme. There is a compelling need for representative models of this critical interface...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28176881/functional-coupling-of-human-microphysiology-systems-intestine-liver-kidney-proximal-tubule-blood-brain-barrier-and-skeletal-muscle
#20
Lawrence Vernetti, Albert Gough, Nicholas Baetz, Sarah Blutt, James R Broughman, Jacquelyn A Brown, Jennifer Foulke-Abel, Nesrin Hasan, Julie In, Edward Kelly, Olga Kovbasnjuk, Jonathan Repper, Nina Senutovitch, Janet Stabb, Catherine Yeung, Nick C Zachos, Mark Donowitz, Mary Estes, Jonathan Himmelfarb, George Truskey, John P Wikswo, D Lansing Taylor
Organ interactions resulting from drug, metabolite or xenobiotic transport between organs are key components of human metabolism that impact therapeutic action and toxic side effects. Preclinical animal testing often fails to predict adverse outcomes arising from sequential, multi-organ metabolism of drugs and xenobiotics. Human microphysiological systems (MPS) can model these interactions and are predicted to dramatically improve the efficiency of the drug development process. In this study, five human MPS models were evaluated for functional coupling, defined as the determination of organ interactions via an in vivo-like sequential, organ-to-organ transfer of media...
February 8, 2017: Scientific Reports
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