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https://www.readbyqxmd.com/read/27883356/a-human-brain-microphysiological-system-derived-from-induced-pluripotent-stem-cells-to-study-neurological-diseases-and-toxicity
#1
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/27846345/systems-biology-for-organotypic-cell-cultures
#2
Sonia Grego, Edward R Dougherty, Francis J Alexander, Scott S Auerbach, Brian R Berridge, Michael L Bittner, Warren Casey, Philip C Cooley, Ajit Dash, Stephen S Ferguson, Timothy R Fennell, Brian T Hawkins, Anthony J Hickey, Andre Kleensang, Michael N J Liebman, Florian Martin, Elizabeth A Maull, Jason Paragas, Guilin Gary Qiao, Sreenivasa Ramaiahgari, Susan J Sumner, Miyoung Yoon
Translating in vitro biological data into actionable information related to human health holds the potential to improve disease treatment and risk assessment of chemical exposures. While genomics has identified regulatory pathways at the cellular level, translation to the organism level requires a multiscale approach accounting for intra-cellular regulation, inter-cellular interaction, and tissue/organ-level effects. Tissue-level effects can now be probed in vitro thanks to recently developed systems of three-dimensional (3D), multicellular, "organotypic" cell cultures, which mimic functional responses of living tissue...
November 14, 2016: ALTEX
https://www.readbyqxmd.com/read/27831629/alternative-acute-oral-toxicity-assessment-under-reach-based-on-sub-acute-toxicity-values
#3
Andrea Gissi, Kimmo Louekari, Laurence Hoffstadt, Norbert Bornatowicz, Alberto Martin Aparicio
The REACH Regulation requires information on acute oral toxicity for substances produced or imported in quantities greater than one tonne per year. When registering, animal testing should be used as last resort. The standard acute oral toxicity test requires use of animals. Therefore, the European Chemicals Agency examined whether alternative ways exist to generate information on acute oral toxicity. The starting hypothesis was that low acute oral toxicity can be predicted from the results of low toxicity in oral sub-acute toxicity studies...
November 8, 2016: ALTEX
https://www.readbyqxmd.com/read/27776202/uncertainties-of-testing-methods-what-do-we-want-to-know-about-carcinogenicity
#4
Martin Paparella, Annamaria Colacci, Miriam N Jacobs
An approach for a systematic description of the uncertainties and complexity of the standard animal testing and assessment approach for carcinogenicity is explored by using a draft OECD Guidance document that was originally developed for reporting defined in vitro approaches to testing and assessment (OECD, 2016). The format is suitable for this re-purposing and it appears that the potential multitude of approaches for integrating and interpreting data from standard animal testing may ultimately be conceptually similar to the challenge of integrating relevant in vitro and in silico data...
October 24, 2016: ALTEX
https://www.readbyqxmd.com/read/27768805/ex-vivo-culture-platform-for-assessment-of-cartilage-repair-treatment-strategies
#5
Andrea Schwab, Annick Meeuwsen, Franziska Ehlicke, Jan Hansmann, Lars Mulder, Anthal Smits, Heike Walles, Linda Kock
There is a great need for valuable ex vivo models that allow for assessment of cartilage repair strategies to reduce the high number of animal experiments. In this paper we present three studies with our novel ex vivo osteochondral culture platform. It consists of two separated media compartments for cartilage and bone which better represents the in vivo situation and enables supply of specific factors to the different needs of bone and cartilage. We investigated whether separation of the cartilage and bone compartments and/or culture media results in the maintenance of viability, structural and functional properties of cartilage tissue (study A)...
October 21, 2016: ALTEX
https://www.readbyqxmd.com/read/27768804/keratinocytes-improve-prediction-of-sensitization-potential-and-potency-of-chemicals-with-thp-1-cells
#6
Jennifer Hennen, Brunhilde Blömeke
In vitro approaches address key steps of chemical-induced skin sensitization but there is uncertainty how keratinocytes, which play a crucial role not only regarding xenobiotic metabolism but also skin inflammation, impact on chemicals' potential and potency of dendritic cell activation. We investigated these aspects by coculturing THP-1 cells, as surrogate dendritic cells, with HaCaT keratinocytes. We tested our HaCaT/THP-1 model with a set of 14 sensitizers, containing 7 prohaptens, and 10 non-sensitizers...
October 21, 2016: ALTEX
https://www.readbyqxmd.com/read/27768803/human-environmental-disease-network-a-computational-model-to-assess-toxicology-of-contaminants
#7
Olivier Taboureau, Karine Audouze
During the past decades, many epidemiological, toxicological and biological studies have been performed to assess the role of environmental chemicals as potential toxicants for diverse human disorders. However, the relationships between diseases based on chemical exposure have been rarely studied by computational biology. We developed a human environmental disease network (EDN) to explore and suggest novel disease-disease and chemical-disease relationships. The presented scored EDN model is built upon the integration on systems biology and chemical toxicology using chemical contaminants information and their disease relationships from the reported TDDB database...
October 21, 2016: ALTEX
https://www.readbyqxmd.com/read/27725990/in-vitro-chemotaxis-and-tissue-remodeling-assays-quantitatively-characterize-foreign-body-reaction
#8
Maren Jannasch, Tobias Weigel, Lisa Engelhardt, Judith Wiezoreck, Sabine Gaetzner, Heike Walles, Tobias Schmitz, Jan Hansmann
Surgical implantation of a biomaterial triggers foreign-body-induced fibrous encapsulation. Two major mechanisms of this complex physiological process are (I) chemotaxis of fibroblasts from surrounding tissue to the implant region, followed by (II) tissue remodeling. As an alternative to animal studies, we here propose anprocess-aligned in vitrotest platform to investigate the material dependency of fibroblast chemotaxis and tissue remodeling, mediated by material-resident macrophages. Embedded in a biomimetic three-dimensional collagen hydrogel, chemotaxis of fibroblasts in direction of macrophage-material-incubated cell culture supernatant was analysed by live-cell imaging...
October 11, 2016: ALTEX
https://www.readbyqxmd.com/read/27725989/behavior-of-laboratory-dogs-before-and-after-rehoming-in-private-homes
#9
Dorothea Döring, Ophelia Nick, Alexander Bauer, Helmut Küchenhoff, Michael H Erhard
Although the rehoming of laboratory dogs has gained importance, scientific data that evaluate the process are lacking. Therefore, 145 laboratory beagles were tested before leaving the research facility (Test 1). The new owners were surveyed using a standardized telephone interview 1 week (n = 143) and 12 weeks (n = 126) after adoption. The behavior test was repeated with 68 dogs in their new homes 6 weeks after adoption (Test 2). The predictive power of Test 1 as well as the relevance of various factors was analyzed...
October 11, 2016: ALTEX
https://www.readbyqxmd.com/read/27690270/hepatotoxicity-prediction-by-systems-biology-modeling-of-disturbed-metabolic-pathways-using-gene-expression-data
#10
Pablo Carbonell, Oriol Lopez, Alexander Amberg, Manuel Pastor, Ferran Sanz
The present study applies a systems biology approach for the in silico predictive modeling of drug toxicity on the basis of high-quality preclinical drug toxicity data with the aim of increasing the mechanistic understanding of toxic effects of compounds at different levels (pathway, cell, tissue, organ). The model development has been carried out using 77 compounds for which gene expression data are available in the LINCS database for primary human hepatocytes treated with the compounds, as well as rodent in vivo hepatotoxicity information is available in the eTOX database...
September 30, 2016: ALTEX
https://www.readbyqxmd.com/read/27684074/toward-achieving-harmonization-in-a-nano-cytotoxicity-assay-measurement-through-an-interlaboratory-comparison-study
#11
John T Elliott, Matthias Rösslein, Nam Woong Song, Blaza Toman, Agnieszka Kinsner-Ovaskainen, Rawiwan Maniratanachote, Marc L Salit, Elijah J Petersen, Fatima Sequeira, Erica L Romsos, Soo Jin Kim, Jieun Lee, Nadia R Von Moos, François Rossi, Cordula Hirsch, Harald F Krug, Wongsakorn Suchaoin, Peter Wick
Design and development of reliable cell-based nanotoxicology assays are important for evaluation of potentially hazardous engineered nanomaterials. Challenges to producing a reliable assay protocol include working with nanoparticle dispersions and living cell lines, and the potential for nano-related interference effects. Here we demonstrate the use of a 96-well plate design with several measurement controls and an interlaboratory comparison study involving five laboratories to characterize the robustness of a nano-cytotoxicity MTS cell viability assay...
September 29, 2016: ALTEX
https://www.readbyqxmd.com/read/27667476/replacing-reducing-and-refining-the-use-of-animals-in-tuberculosis-vaccine-research
#12
Rachel Tanner, Helen McShane
Tuberculosis (TB) remains a serious global health threat and an improved vaccine is urgently needed. New candidate TB vaccines are tested using preclinical animal models such as mice, guinea pigs, cattle and non-human primates. Animals are routinely infected with virulent Mycobacterium tuberculosis (M.tb) in challenge experiments to evaluate protective efficacy, raising ethical issues regarding the procedure of infection itself, symptoms of disease and humane end-points. We summarise the importance and limitations of animal models in TB vaccine research and review current alternatives and modifications in the context of the NC3Rs framework for replacing, reducing and refining the use of animals for scientific purposes...
September 26, 2016: ALTEX
https://www.readbyqxmd.com/read/27554434/good-cell-culture-practice-for-stem-cells-and-stem-cell-derived-models
#13
David Pamies, Anna Bal-Price, Anton Simeonov, Danilo Tagle, Dave Allen, David Gerhold, Dezhong Yin, Francesca Pistollato, Takashi Inutsuka, Kristie Sullivan, Glyn Stacey, Harry Salem, Marcel Leist, Mardas Daneshian, Mohan C Vemuri, Richard McFarland, Sandra Coecke, Suzanne C Fitzpatrick, Uma Lakshmipathy, Amanda Mack, Wen Bo Wang, Yamazaki Daiju, Yuko Sekino, Yasunari Kanda, Lena Smirnova, Thomas Hartung
The first guidance on Good Cell Culture Practice dates back to 2005. This document expands this to aspects of quality assurance for in vitro cell culture focusing on the increasingly diverse cell types and culture formats used in research, product development, testing and manufacture of biotechnology products and cell-based medicines. It provides a set of basic principles of best practice which can be used in training new personnel, reviewing and improving local procedures, and helping to assure standard practices and conditions for the comparison of data between laboratories and experimentation performed at different times...
August 23, 2016: ALTEX
https://www.readbyqxmd.com/read/27463612/design-of-a-high-throughput-human-neural-crest-cell-migration-assay-to-indicate-potential-developmental-toxicants
#14
Johanna Nyffeler, Christiaan Karreman, Heidrun Leisner, Yong Jun Kim, Gabsang Lee, Tanja Waldmann, Marcel Leist
Migration of neural crest cells (NCCs) is one of the pivotal processes of human fetal development. Malformations arise, if NCC migration and differentiation are impaired genetically or by toxicants. In the currently available test systems for migration inhibition of NCC (MINC), the manual generation of a cell-free space results in extreme operator dependencies, and limits throughput. Therefore, a new test format was established here. The assay avoids scratching by plating cells around a commercially available circular stopper...
July 27, 2016: ALTEX
https://www.readbyqxmd.com/read/27452664/reference-compounds-for-alternative-test-methods-to-indicate-developmental-neurotoxicity-dnt-potential-of-chemicals-example-lists-and-criteria-for-their-selection-and-use
#15
Michael Aschner, Sandra Ceccatelli, Mardas Daneshian, Ellen Fritsche, Nina Hasiwa, Thomas Hartung, Helena T Hogberg, Marcel Leist, Abby Li, William R Mundi, Stephanie Padilla, Aldert H Piersma, Anna Bal-Price, Andrea Seiler, Remco H Westerink, Bastian Zimmer, Pamela J Lein
There is a paucity of information concerning the developmental neurotoxicity (DNT) hazard posed by industrial and environmental chemicals. New testing approaches will most likely be based on batteries of alternative and complementary (non-animal) tests. As DNT is assumed to result from the modulation of fundamental neurodevelopmental processes (such as neuronal differentiation, precursor cell migration or neuronal network formation) by chemicals, the first generation of alternative DNT tests target these processes...
July 25, 2016: ALTEX
https://www.readbyqxmd.com/read/27442998/assigning-ethical-weights-to-clinical-signs-observed-during-toxicity-testing
#16
Joakim Ringblom, Elin Törnqvist, Sven Ove Hansson, Christina Rudén, Mattias Öberg
Reducing the number of laboratory animals used and refining experimental procedures to enhance animal welfare are fundamental questions to be considered in connection with animal experimentation. Here, we explored the use of cardinal ethical weights for clinical signs and symptoms in rodents by conducting Trade-Off interviews with members of Swedish Animal Ethics Committees in order to derive such weights for nine typical clinical signs of toxicity. The participants interviewed represent researchers, politically nominated laypersons and representatives of animal welfare organizations...
July 21, 2016: ALTEX
https://www.readbyqxmd.com/read/27388676/3-d-nasal-cultures-systems-toxicological-assessment-of-a-candidate-modified-risk-tobacco-product
#17
Anita R Iskandar, Carole Mathis, Florian Martin, Patrice Leroy, Alain Sewer, Shoaib Majeed, Diana Kuehn, Keyur Trivedi, Davide Grandolfo, Maciej Cabanski, Emmanuel Guedj, Celine Merg, Stefan Frentzel, Nikolai V Ivanov, Manuel C Peitsch, Julia Hoeng
In vitro toxicology approaches have evolved, from a focus on molecular changes within a cell to understanding of toxicity-related mechanisms in systems that can mimic the in vivo environment. The recent development of three dimensional (3-D) organotypic nasal epithelial culture models offers a physiologically robust system for studying the effects of exposure through inhalation. Exposure to cigarette smoke (CS) is associated with nasal inflammation; thus the nasal epithelium is relevant for evaluating the pathophysiological impact of CS exposure...
July 7, 2016: ALTEX
https://www.readbyqxmd.com/read/27328013/advancing-toxicology-research-using-in-vivo-high-throughput-toxicology-with-small-fish-models
#18
Antonio Planchart, Carolyn J Mattingly, David Allen, Patricia Ceger, Warren Casey, David Hinton, Jyotshna Kanungo, Seth W Kullman, Tamara Tal, Maria Bondesson, Shawn M Burgess, Con Sullivan, Carol Kim, Mamta Behl, Stephanie Padilla, David M Reif, Robert L Tanguay, Jon Hamm
Small freshwater fish models, especially zebrafish,offer advantages over traditional rodent models, including low maintenance and husbandry costs, high fecundity, genetic diversity, physiology similar to that of traditional biomedical models, and reduced animal welfare concerns. The Collaborative Workshop on Aquatic Models and 21st Century Toxicology was held at North Carolina State University on May 5-6, 2014, in Raleigh, North Carolina, USA. Participants discussed the ways in which small fish are being used as models to screen toxicants and understand mechanisms of toxicity...
June 21, 2016: ALTEX
https://www.readbyqxmd.com/read/27254273/bridging-the-gap-between-regulatory-acceptance-and-industry-use-of-non-animal-methods
#19
Amy J Clippinger, Erin Hill, Rodger Curren, Patricia Bishop
Collaboration between industry and regulators resulted in the development of a decision tree approach using in vitro or ex vivo assays to replace animal tests when determining the eye irritation potential of antimicrobial cleaning products (AMCPs) under the United States Environmental Protection Agency (EPA) Office of Pesticide Programs' hazard classification and labeling system. A policy document issued by the EPA in 2013 and updated in 2015 describes the alternate testing framework that industry could apply to new registrations of AMCPs and, on a case-by-case basis, to conventional pesticide products...
June 2, 2016: ALTEX
https://www.readbyqxmd.com/read/27196738/mutz-3-langerhans-cell-maturation-and-cxcl12-independent-migration-in-reconstructed-human-gingiva
#20
Ilona J Kosten, Sander W Spiekstra, Tanja D de Gruijl, Susan Gibbs
Here we describe a reconstructed full thickness human oral mucosa (gingiva) equivalent with integrated Langerhans Cells (GE-LC) and use it to compare LC activation and migration from oral versus skin epithelium. The physiologically representative models consist of differentiated reconstructed epithelium (keratinocytes and Langerhans-like cells derived from the MUTZ-3 cell line) on a fibroblast-populated collagen hydrogel which serves as a lamina propria for gingiva and dermis for skin. Topical exposure of GE-LC and the skin equivalent (SE-LC) to sub-toxic concentrations of the allergens cinnamaldehyde, resorcinol and nickel sulphate, resulted in LC migration out of the epithelia...
May 19, 2016: ALTEX
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