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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
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
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
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
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
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
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
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 Westerink, Bastian Zimmer, Pamela 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
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
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
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
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
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
Florian Groeber, Lisa Engelhardt, Julia Lange, Szymon Kurdyn, Freia F Schmid, Christoph Rücker, Stephan Mielke, Heike Walles, Jan Hansmann
Tissue-engineered skin equivalents mimic key aspects of the human skin, and can thus be employed as wound coverage for large skin defects or as in vitro test systems as an alternative to animal models. However, current skin equivalents lack a functional vasculature limiting clinical and research applications. This study demonstrates the generation of a vascularized skin equivalent with a perfused vascular network by combining a biological vascularized scaffold (BioVaSc) based on a decellularized segment of a porcine jejunum and a tailored bioreactor system...
May 15, 2016: ALTEX
Joaquín Valdés, Laura Trachsel-Moncho, Ayse Sahaboglu, Dragana Trifunović, María Miranda, Marius Ueffing, François Paquet-Durand, Oliver Schmachtenberg
Diabetic retinopathy (DR) is a major cause of vision loss and one of the most common and debilitating complications of diabetes. Research to prevent DR is hindered by a lack of experimental model systems that faithfully reproduce the disease pathology, in particular for type 2 diabetes, which requires prolonged disease progression in animals to develop some hallmarks of DR. Here, we introduce an alternative in vitro model system for DR, based on serum-free, organotypic rodent retinal explant cultures, which allow physiological and pharmacological manipulation of the retina for up to two weeks under tightly controlled conditions...
May 9, 2016: ALTEX
Cédric Pisani, Sébastien Voisin, Karim Arafah, Philippe Durand, Marie-Hélène Perrard Perrard, Marie-Roberte Guichaoua, Philippe Bulet, Odette Prat
To measure the testicular toxicity of two fungicides (carbendazim and iprodione), alone or in a mixture, we used a rat ex vivo model of seminiferous tubules, greatly reducing the number of rodents used, in accordance with the 3R rule (Replacement, Reduction, and Refinement). This model allows the representation of puberty, a critical life period with regard to endocrine disruptors. The cellular modifications were followed for three weeks through transcriptomic and proteomic profiling analysis. A quantitative and comparative method was developed to estimate how known pathways were disturbed by each substance...
May 8, 2016: ALTEX
Miriam N Jacobs, Annamaria Colacci, Kimmo Louekari, Mirjam Luijten, Betty C Hakkert, Martin Paparella, Paule Vasseur
Although regulatory requirements for carcinogenicity testing of chemicals vary according to product sector and regulatory jurisdiction, the standard approach starts with a battery of genotoxicity tests. If any of the in vivo genotoxicity tests are positive, a lifetime rodent cancer bioassay may be requested, which allows the detection of non-genotoxic carcinogens (NGTxC). However, under most chemical regulations the cancer bioassay is rarely requested, specific requests to obtain information on non-genotoxic mechanisms of carcinogenicity are few, and there are no OECD approved screening methods...
April 27, 2016: ALTEX
Alexandra Maertens, Bruno Hubesch, Costanza Rovida
No abstract text is available yet for this article.
2016: ALTEX
Cristina Barbosa da Silva, Gabriel Martins, Walter Lilenbaum
No abstract text is available yet for this article.
2016: ALTEX
Thomas Hartung
E-cigarettes have become within only one decade an important commodity, changing the market of the most mass-killing commercial product. While a few years ago estimates suggested that in the course of the 21st century one billion people would die prematurely from tobacco consumption, e-cigarettes continuously gaining popularity promise 10-30fold lower health effects, possibly strongly changing this equation. However, they still are not a harmless life-style drug. Acceptability simply depends on whether we compare their use to smoking or to not-smoking...
2016: ALTEX
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