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Elly Hol (UMC Utrecht): possibilities for neuroscience
Expert interviews
HealthInnovation

Elly Hol (UMC Utrecht): possibilities for neuroscience

Prof. dr. Elly Hol (neuroscientist) talks about the opportunities for conducting animal-free research in Utrecht. She explains why it is necessary to use animal models next to cell-based models, for example for her Alzheimer research.
00:593 years ago
Stem cell differentiation assays for animal-free developmental neurotoxicity assessment
Innovation examples
ToxicologyInnovationIn vitro

Stem cell differentiation assays for animal-free developmental neurotoxicity assessment

Victoria de Leeuw was a PhD candidate in the research group of prof. dr. Aldert Piersma at the RIVM and Institute for Risk Assessment Sciences at Utrecht University. Piersma's lab studies the effects of compounds on development of the embryo during pregnancy with, among other techniques, stem cell cultures. The project of Victoria was aimed to differentiate embryonic stem cells of mouse and human origin into neuronal and glial cells, which could mimic parts of differentiation as seen during embryonic brain development. These models were able to show some of the known toxic mechanisms induced by these compounds, congruent with what they we hypothesised to mimic. This provides mechanistic information into how chemical compounds can be toxic to brain development. Therefore, these two stem cell assays make a useful contribution to the animal-free assessment of developmental neurotoxicity potential of compounds. Victoria is nominated for the Hugo van Poelgeest prize 2022 for excellent research to replace animal testing.
00:4316 months ago
New approaches for cancer hazard assessment
Innovation examples

New approaches for cancer hazard assessment

Chemical substances are subjected to assessment of genotoxic and carcinogenic effects before being marketed to protect man and the environment from health risks. For cancer hazard assessment, the long-term rodent carcinogenicity study is the current mainstay for the detection of nongenotoxic carcinogens. However, carcinogenicity studies are shown to have prominent weaknesses and are subject to ethical and scientific debate. A transition toward a mechanism-based weight of evidence approach is considered a requirement to enhance the prediction of carcinogenic potential for chemicals. At RIVM, we are working on this alternative approach for cancer hazard assessment, which makes optimal use of innovative (computational) tools and be less animal demanding. For more information, click on the link in the video or read on here (https://doi.org/10.1080/10408444.2020.1841732) and here (https://doi.org/10.1080/10408444.2018.1458818). Contact the expert (https://nl.linkedin.com/in/mirjamluijten)
03:1449 days ago
Erwin Roggen (ToxGenSolutions)
Expert interviews
ToxicologyIn vitro

Erwin Roggen (ToxGenSolutions)

ToxGenSolutions provides a cutting-edge patchwork of test methods required for modern testing and assessment of compounds and products. It builds on a virtual generic platform of leading test and technology developers providing novel technologies addressing key events in outcome pathways. ToxGenSolutions products are proprietary mechanism-based gene signatures for identification and classification of toxicants during screening, product development and safety assessment. More information on https://toxgensolutions.eu/ .
01:074 years ago
Cartilage-on-a-chip for studying joint degenerative diseases
Innovation examples
ToxicologyInnovationIn vitro

Cartilage-on-a-chip for studying joint degenerative diseases

Carlo Alberto Paggi is currently a PhD candidate at the University of Twente in the research group of Prof. Marcel Karperien and Prof. Séverine Le Gac. Karperien’s lab focus on the biological aspects of osteoarthritic research while Le Gac’s specialize in organ-on-chip development. The project of Carlo Alberto is developing a joint-on-chip platform to create a reliable in vitro model to study disease progression in osteo- or rheumatoid arthritis. The model combines different organ-on-chips aimed at replicating each a tissue around the joint such as cartilage, bone and ligaments. This new technology focuses on better reproducing human models and at substituting the use of animal models for drug research. If you want to know something more about the project and the groups, you can follow the link in the video. Carlo Paggi was nominated for the Hugo van Poelgeest prize for his research on a cartilage-on-a-chip model to study joint degenerative diseases Karperien’s lab of Developmental Bioengineering: https://www.utwente.nl/en/tnw/dbe/ Le Gac’s lab of Applied Microfluidics for BioEngineering Research: http://www.severinelegac.com/ Linkedin: https://www.linkedin.com/in/carlo-alberto-paggi-76500b135/
01:582 years ago
Tony Kiuru (UPM Biomedicals)
Expert interviews
HealthIn vitro

Tony Kiuru (UPM Biomedicals)

Tony Kiuru discusses GrowDex, which is an animal free, ready to use hydrogel that mimics the extracellular matrix (ECM) and supports cell growth and differentiation with consistent results. Bridging the gap between in vitro and in vivo studies GrowDex can be used for 3D cell culture for spheroid and /organoids, in personalised medicine, regenerative medicine, organ-on-a-chip models, drug release studies, 3D printing and much more. GrowDex hydrogel is manufactured according to ISO13485. You can find more information about GrowDex at https://www.upmbiomedicals.com/siteassets/documents/growdex-brochure-2018.pdf and https://www.linkedin.com/company/growdex/ . General email address: biomedicals@upm.com.
01:114 years ago
Biotransformation of two proteratogenic anti-epileptics in the zebrafish (Danio rerio) embryo
Conferences abstracts

Biotransformation of two proteratogenic anti-epileptics in the zebrafish (Danio rerio) embryo

The zebrafish (Danio rerio) embryo has gained interest as an alternative model for developmental toxicity testing, which still mainly relies on in vivo mammalian models (e.g., rat, rabbit). However, cytochrome P450 (CYP)-mediated drug metabolism, which is critical for the bioactivation of several proteratogens, is still under debate for this model. Therefore, we investigated the potential capacity of zebrafish embryos/larvae to bioactivate two known mammalian proteratogens, carbamazepine (CBZ) and phenytoin (PHE) into their mammalian active metabolites, carbamazepine-10,11-epoxide (E-CBZ) and 5-(4-hydroxyphenyl)-5-phenylhydantoin (HPPH), respectively. Zebrafish embryos were exposed to three concentrations (31.25, 85, and 250 μM) of CBZ and PHE from 51⁄4 to 120 hours post fertilization (hpf) at 28.5°C under a 14/10 hour light/dark cycle. For species comparison, also adult zebrafish, rat, rabbit and human liver microsomes (200 μg/ml) were exposed to 100 μM of CBZ or PHE for 240 minutes at 28.5°C. Potential formation of the mammalian metabolites was assessed in the embryo medium (48, 96, and 120 hpf); pooled (n=20) whole embryos/larvae extracts (24 and 120 hpf); and in the microsomal reaction mixtures (at 5 and 240 minutes) by targeted investigation using a UPLC–Triple Quadrupole MS system with lamotrigine (0.39 μM) as internal standard. Our study showed that zebrafish embryos metabolize CBZ to E-CBZ, but only at the end of organogenesis (from 96 hpf onwards), and no biotransformation of PHE to HPPH occurred. In contrast, our in vitro drug metabolism assay showed that adult zebrafish metabolize both compounds into their active mammalian metabolites. However, significant differences in metabolic rate were observed among the investigated species. These results highlight the importance of including the zebrafish in the in vitro drug metabolism testing battery for accurate species selection in toxicity studies.
02:572 years ago
Transition Project towards Animal-free Innovations
Projects and initiatives

Transition Project towards Animal-free Innovations

Animal-free innovations are emerging at a fast pace. TPI Chair Daniela Salvatori, and TPI ambassadors Jeffrey Beekman and Elly Hol, explain why animal-free innovations are important and how TPI supports researchers in finding or developing animal-free methods for their research. They call for collaboration.
02:152 years ago
Platform for in vitro airborne inhalation testing
Innovation examples
HealthToxicologyInnovationIn vitro

Platform for in vitro airborne inhalation testing

The air-liquid interface (ALI) technique uses lung cells cultured on a tiny polymer membrane in a cup. On one side of the membrane is a liquid containing the medium necessary for the cells to survive, while the other side is in contact with air. This is similar to the situation in the human lung. The compound to be tested is administered via an aerosol, vapor, or gas to mimic the situation in human lungs. By monitoring different parameters in the cell model before and after the compound is added, it is possible to measure the effects on lung cells. Depending on the test to be carried out, the lung cells can come from different regions in the respiratory tract and even from a variety of people, including individuals who smoke a lot or have specific diseases such as chronic obstructive pulmonary disease or asthma. In vitro ALI inhalation testing (https://doi.org/10.1021/acs.est.7b00493) adds value for e.g. pre-clinical trials and research in the pharmaceutical industry and testing (new) compounds for the chemical sector and beyond. The advantages of ALI inhalation testing are that it is a non-animal method, it reduces the use of in vivo experiments, pre-clinical testing with human-derived cell models is more realistic and limits clinical trial failures and it provides faster and more efficient testing of compound
04:139 months ago
Development of 3D liver spheroids
Innovation examples
HealthToxicologyInnovationIn vitro

Development of 3D liver spheroids

Human-based in vitro models are increasingly being used in the hepatology field. And in addition to the obvious ethical arguments, they offer several advantages over the classical animal models. One of them is the ability to perform mechanistic research at the molecular level in a well-controlled setting and reduce species differences. These liver-based in vitro models can range from simple monolayer cultures of hepatocytes to the liver-on-chips systems in which all liver cells are cultured in a 3D configuration on a microfluidic platform. Liver-based in vitro models must be selected on a case-by-case basis and should fit the purpose of the research, which might go from fundamental to translational research.
01:049 months ago
Helpathon #10 – Can you help Jolanda and Elza?
Meeting videos
HelpathonsEducation

Helpathon #10 – Can you help Jolanda and Elza?

Jolanda van der Velden, Chair of Physiology, and Elza van Deel, Educator, from Amsterdam University Medical Center want to support PhDs in preparing for the animal-free transition. They are both looking for an implementation strategy and course design. Do you have an interest in animal-free education and education about animal-free research? Read more and register here (https://www.helpathonhotel.org/coming-up).
00:5553 days ago
Five simple tricks for making your own video for TPI.tv
Various subjects

Five simple tricks for making your own video for TPI.tv

This video shows you how to make a video yourself. It's really not that difficult! See also https://tpi.tv/how-to-submit for additional information.
01:233 years ago