Innovation examples

Tumor-on-chips to study delivery of protein therapeutics
Innovation examples
HealthInnovationIn vitro

Tumor-on-chips to study delivery of protein therapeutics

Valentina is a PhD candidate at the Department of Biochemistry at Radboudumc. Her research focuses on developing and applying organ-on-chip technologies, such as tumor-on-a-chip systems, to study the tissue-specific and cytosolic delivery of protein therapeutics. Valentina's research has also aimed at bridging the gap between engineers and biologists, promoting the use of microfluidic organ-on-chip technologies to answer more relevant biological questions. One example of this is the development of a mathematical model that could be applied to study drug delivery and diffusion in a tumor-on-a-chip system and to extrapolate possible outcomes of the delivery of therapeutic proteins to tumors in the human body. Another collaboration led to the development of a tumor-on-a-chip where hypoxic conditions can be replicated and investigated, and where the targeting of specific hypoxia markers in tumor cells can be investigated.
00:4743 days 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.
00:4344 days ago
Immortalized human cells to model atrial fibrillation in vitro
Innovation examples
HealthInnovationIn vitro

Immortalized human cells to model atrial fibrillation in vitro

Niels Harlaar is a PhD Candidate at the Laboratory of Experimental Cardiology at the Leiden University Medical Center. Here, under the supervison of prof. dr. D.A. Pijnappels and dr. A.A.F. de Vries, he focusses on the conditional immortalization of human atrial cardiomyocytes for (among many other applications) in vitro modelling of atrial fibrillation. He has successfully generated, characterized and applied this technique of these conditionally immortalized human atrial myocyte lines to model atrial fibrillation in vitro. Niels is nominated for the Hugo van Poelgeest prize 2022 for excellent research to replace animal testing. Click here (https://hartlongcentrum.nl/research/laboratory-of-experimental-cardiology/) for more information on the Laboratory of Experimental Cardiology.
00:4044 days 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)
03:145 months ago
Zebrafish in toxicity testing
Innovation examples

Zebrafish in toxicity testing

Zebrafish are increasingly recognised as a useful model for toxicity testing of chemical substances. Testing strategies are becoming more based on mechanisms of toxicity structured in adverse outcome pathways describing the chain of events leading to toxicity or disease. Using a battery of dedicated in vitro and in silico assays, insight can be gained in how exposure leads to disease. For certain diseases it is known that toxicity relies on the interaction between different organs and cell types, which requires research on whole organisms in addition to simple in vitro models. The zebrafish is considered a valuable whole organism model in a mechanism-based testing strategy. At RIVM, the zebrafish embryo model is used for testing the effect of chemical substances on several adverse outcomes and diseases. For more information see: https://ehp.niehs.nih.gov/doi/10.1289/EHP9888; https://doi.org/10.3390/ijerph18136717; www.linkedin.com/in/harm-heusinkveld
03:015 months ago
Animal-free computational modelling for prevention of human chemical-induced neural tube defects
Innovation examples

Animal-free computational modelling for prevention of human chemical-induced neural tube defects

Animal-free methods for human chemical safety assessment are promising tools for the reduction of animal testing. However, these methods only measure a small aspect of biology compared to an in vivo test. The reductionist nature of these methods thus limits their individual application in the regulatory arena of chemical risk assessment. Ontologies can be used to describe human biology, and delineate the basis of adverse outcome pathway networks that describe how chemical exposures may lead to adverse health effects. This pathway description can then help to select animal-free in vitro and in silico methods, comprehensively covering the network. The comprehensiveness of this approach, firmly rooted in human biology, is expected to facilitate regulatory acceptance of animal-free methods. As an example, this video zooms in on the development of a computational model for neural tube development, an aspect of human development that is especially vulnerable to chemical disruption. This research is part of the ONTOX project (https://www.ontox-project.eu). For more information on the concept of the Virtual Human, click here (https://doi.org/10.1016/j.cotox.2019.03.009.).
03:057 months ago
Developmental neurotoxicity testing using stem cells
Innovation examples

Developmental neurotoxicity testing using stem cells

Children should grow up in a safe and healthy environment. Disruption of brain development may have enormous impact on future life and might result in disorders such as ADHD or cognitive decline. The effect of compound exposure on the developing brain is largely unknown, since in the current regulatory test procedures in experimental animals effects on the brain are rarely investigated and human relevance of these animal models is under debate. Researchers at RIVM are developing a cell model based on human stem cells that mimics a small part of the developing brain. This method is human-relevant, animal-free, and based on mechanistic knowledge of human biology and physiology of brain development. The model can be an important component in a testing strategy to test the safety of chemicals and pharmaceuticals on the developing brain.
02:277 months ago
Understanding implant safety in vitro
Innovation examples

Understanding implant safety in vitro

Each year, millions of people receive an implant. The function of damaged tissues or organs is successfully restored in most people, however, some do develop complications. The safety of medical devices is indicated for legislation using international regulations. In the relevant standards, tests mainly focus on the chemical nature of the implants using classical toxicological end-points. However, more recently we have learned that the mechanical forces from an implant on the host-tissue can have significant effects on the host-response as well. At RIVM we want to develop an animal-free model that better resembles the interface between the implant and the host-tissue, and by updating the testing strategies contribute to implant safety on the long term.
03:049 months ago
Respiratory toxicity using in vitro methods
Innovation examples

Respiratory toxicity using in vitro methods

The airways form a barrier for inhaled compounds, however, such compounds may cause local effects in the airways or may lead to lung diseases, such as fibrosis or COPD. Cell models of the respiratory tract, cultured at the air-liquid-interface (ALI) are a relevant model to assess the effects of inhaled compounds on the airways. Such models allow human relevant exposure, which is via the air, and assessment of effects on the epithelial cell layer. At RIVM we use air-liquid-interface cultured cell models and expose these to airborne compounds to assess the effects of agents such as nanomaterials, air pollutants or compounds from cigarette smoke. By using a mechanism-based approach to assess the effects of these compounds we invest in animal-free alternatives that better predict adverse effects in humans.
02:2412 months ago
FirstbaseBIO - human brain organoids for studying neurological diseases
Innovation examples
HealthInnovationIn vitro

FirstbaseBIO - human brain organoids for studying neurological diseases

Human neurological diseases are still poorly understood, amongst others because animals are used as a model for the human brain. A way to overcome this problem is to mimic human brain functioning in a dish with organoids. FirstbaseBIO is developing off-the-shelf brain organoids on which neurological diseases can be studied. This 3D platform will be formed by reprogrammed human cells from easily accessible sources, for example urine, skin, or mucosa. The proof of-concept brain organoids will be those from patients who are suffering from adrenoleukodystrophy (ALD), a rare, incurable brain disease that occurs primarily in young boys and is often fatal. With the brain organoid platform, possible medicinal treatments for ALD can be effectively optimised. FirstbaseBIO was nominated for the Venture Challenge 2021 for their development of human brain organoids to study neurological diseases.
03:3318 months ago
GUTS BV - small intestine-on-a-chip and advanced computational analysis for compound and protein screening
Innovation examples
HealthToxicologyIn vitro

GUTS BV - small intestine-on-a-chip and advanced computational analysis for compound and protein screening

GUTS BV is a contract research organization offering its 3-dimensional state-of-the-art small intestinal in vitro model in combination with custom computational analysis approaches. The small intestinal model was developed during Dr. Paul Jochems PhD research at Utrecht University in the group of Prof. Roos Masereeuw. In comparison to the current gold standard (Transwell model), they show improvement in cell differentiation (all major specialized cell types present), physiological structure (3D tube- and villi-like structures) and a functional epithelial barrier. After acquiring experimental data from this model computational analysis approaches are used to score and compare measured compounds for all tested biological parameters at once. The combined effort of improved in vitro modelling and data analysis is believed to result in an enhanced preclinical predictability. GUTS BV was nominated for the Venture Challenge 2021 for their development of an intestinal model combined with advanced computational analysis for protein and chemical compound screening. Research papers: https://www.sciencedirect.com/science/article/pii/S0887233318307811 https://www.mdpi.com/2072-6643/12/9/2782/htm https://www.nature.com/articles/s41538-020-00082-z LinkedIn: https://www.linkedin.com/company/71016128/
02:1118 months ago
Avatar Zoo - teaching animal anatomy using virtual reality
Innovation examples
EducationInnovation

Avatar Zoo - teaching animal anatomy using virtual reality

Animals are essential to train the next generation of scientists understand diseases and develop treatments for humans as well as animals. Therefore, animals are used for educational purposes. Technologies such as Virtual Reality and Augmented Reality can be employed to reduce the number of animals in the future. Prof. Dr. Daniela Salvatori is working on the development of 'Avatar Zoo' together with UMCU and IT. Live animals are replaced by holographic 3D in this flexible platform. With these holograms one is able to study the anatomical, physiological and pathological systems and processes of all kinds of animals. Avatar Zoo won the Venture Challenge 2021 for the development of virtual reality models that can be used for anatomy classes and practical training.
02:4018 months ago