Experts

Monique Janssens (personal account): Why we need the Transition towards Animal-free Innovations
Expert interviews
HelpathonsPolicy

Monique Janssens (personal account): Why we need the Transition towards Animal-free Innovations

Why is there a Transition towards Animal-free Innovations, while we have the 3Rs, including Replacement? Well, there is a difference. Animal experiments should no longer be the golden standard of reference. We should not ask: Is this animal-free method good enough to replace animal experiments? But: What is the research question, and how do I get the best answer, preferably without animals? I know that many researchers are doing this already. But we can do even more! It’s also about involving the full chain of parties, including patients, financers, legislators and companies. That is why the transition movement works with interdisciplinary networks and Helpathons. The transition helps to innovate, to accelerate and to implement. At the same time, there is no need to throw the 3Rs overboard. Actually, we owe applying them to the lab animals of today. But by innovating we can develop even more new practices in research and education that bring about better results for science in less time and often with less costs. Without using animals.
02:374 months ago
Daniela Salvatori: TPI Utrecht
Expert interviews
HealthEducation

Daniela Salvatori: TPI Utrecht

Prof. dr. Daniela Salvatori, chair of TPI Utrecht, presents the aims of the local TPI group and invites all who want to share their ideas or questions on the transition towards animal-free innovations to get in touch via uu.nl/tpi.
02:2312 months ago
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. More info at https://www.umcutrecht.nl/en/research/center/brain-center , http://translationalneuroscience.nl , http://www.ellyhollab.eu .
00:5913 months ago
Wim de Leeuw: Aim and activities of TPI Utrecht
Expert interviews
EducationInnovation

Wim de Leeuw: Aim and activities of TPI Utrecht

TPI Utrecht facilitates the Utrecht infrastructure to stimulate the transition to animal-free innovation. There is a helpdesk, a group of ambassadors, and a 3Rs Stimulus Fund. A digital marketplace for exchange of tissues is being developed, and as well a hybrid centre for biomedical translation, where there will increasingly be place for animal-free techniques.
01:5615 months ago

Innovation

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.
02:2410 days 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.
03:335 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/
02:115 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.
02:405 months ago

Meetings

Helpathon #4 - can you help Frank?
Meeting videos
HelpathonsHealth

Helpathon #4 - can you help Frank?

Can you help Frank with integrating an immune system into a macaque lung organoid to address local immunity to tuberculosis with his vaccination strategy? Join Helpathon #4, look at www.tpihelpathon.nl/coming-up ! Frank Verreck does research on tuberculosis at the Biomedical Primate Research Center (BPRC). Tuberculosis is the most deadly infectious disease worldwide! For the past hundred years, BCG (Bacillus Calmette Guérin) vaccinations take place through the skin. Research shows that macaques can be better protected from this infection by vaccination through their lungs. Frank really wants to further study the potential of this alternative vaccination strategy. He wants to understand how this BCG vaccination works in macaques lungs.
01:2115 months ago
Helpathon #4 - can you help Raissa?
Meeting videos
HelpathonsIn vitro

Helpathon #4 - can you help Raissa?

Can you help Raissa find a more complex organoid-like brain and immune model based on rhesus microglia to study aging in relation to neuroinflammation and neurodegenerative diseases? Join Helpathon #4, look at www.tpihelpathon.nl/coming-up ! Raissa Timmerman is a PhD student at the alternative unit at the Biomedical Primate Research Center. A better understanding of aging of the brain is key to studying neuroinflammation and neurodegenerative diseases. We believe there is a potential for breakthrough in using our existing live macaque data obtained from past aging experiments to develop more complex in vitro rhesus brain-like models and then to correlate all this data with data from human in vitro models and human live data.
01:3215 months ago
Helpathon #4 - can you help Anne-Marie?
Meeting videos
HelpathonsIn vitro

Helpathon #4 - can you help Anne-Marie?

Can you help Anne-Marie develop a more organ-like Rhesus 3D liver model in which she can study the dormancy and the waking up of malaria parasites? Join Helpathon #4, look at www.tpihelpathon.nl/coming-up ! Anne- Marie Zeeman is a researcher at the Biomedical Primate Research Center (BPRC). Anne-Marie studies recurrent malaria ( P. vivax). She successfully developed a single cell layer in vitro model to study compounds affecting dormant and active malaria parasites in the liver of Rhesus monkeys. We believe that the cross correlation between in vitro Rhesus and in vitro human models will provide the missing link required to improve the drug development process and aid transition. A more refined Rhesus in vitro model can reduce the number of monkeys currently used for testing drugs. The data from in vivo monkeys combined with new in vitro models could help validate and develop reliable human in vitro models making testing on monkeys unnecessary detours.
01:3815 months ago
Sign in for Helpathon #3: Saskia van Mil
Meeting videos
HelpathonsHealth

Sign in for Helpathon #3: Saskia van Mil

Saskia van Mil calls for a Helpathon! She invites you to help her develop a human model for studying liver metabolism? You can sign in for this Helpathon here: tpihelpathon.nl. Online, 18th - 19th of June 2020.
01:1618 months ago

Conferences

Setting up a PDXO platform of pancreatic cancer with spatial -omics characterization
Conferences abstracts

Setting up a PDXO platform of pancreatic cancer with spatial -omics characterization

Pancreatic ductal adenocarcinoma (PDAC) is known for its aggressive biology and lethality. Due to a low success rate of current diagnostic and therapeutic approaches in clinic, there is an urgent need for preclinical research studies to investigate the underlying biology of this malignancy. This knowledge is indispensable to facilitate the development and validation of potential new therapeutic compounds. Superior to conventional biomedical research models, the focus of this study is on the development and use of a well-established patient-derived 3D in vivo model, mimicking the tumor as it is present in a human body. The development and characterization of pancreatic cancer derived organoids. This model is extensively analysed using advanced histological methods omics technology to perform tumor subtyping. 15 established PDAC organoid lines and their corresponding parental tumors are validated using immunostainings and DNA hotspot sequencing. This study is the first to show in situ detection of important driver mutations of pancreatic cancer, like KrasG12D, both in parental tumor and organoids. Additionally, specific culture conditions are defined to develop subtype-specific organoids which are validated using multiplex RNA in situ hybridization and transcriptomics. We are proud to collaborate in a fruitful international project, aiming to set-up a pre-clinical screening platform for pancreatic cancer based on patient-derived organoids -and xenografts. Altogether, spatial-omics in depth analysis of both models will demonstrate (1) high resemblance to parental tissue and (2) subtype-specific signatures associated with type of model. Ultimately, the screening platform can be used by pharmaceutical companies to facilitate oncological drug testing in a subtype specific way. Publications Ilse Rooman's lab: https://pubmed.ncbi.nlm.nih.gov/34330784/ https://pubmed.ncbi.nlm.nih.gov/31161208/
03:2829 days ago
A Decision Support System to Investigate the Medical Management of Ventricular Assist Device Patients
Conferences abstracts

A Decision Support System to Investigate the Medical Management of Ventricular Assist Device Patients

Despite the positive outcomes of ventricular assist device (VAD) therapy, there are still some adverse events, such as suction, caused by the mismatch of the preload of the left ventricle and the flow of the pump. Ventricular suction can be due to multiple underlying pathophysiological conditions. However, the medical management of such patients is still not well defined. In order to analyse the potential of different therapeutic interventions to mitigate suction in different pathophysiological conditions, a suction module is embedded in a cardiovascular hybrid (hydraulic-computational) simulator. The suction module mimics the ventricular apex and its connection with a HeartWare HVAD system (Medtronic). With such a set-up, the medical management of different pathophysiological conditions can be evaluated, without the use of animals. Also watch the video on the cardiovascular simulator used for this research: https://tpi.tv/watch/76 Contact: https://www.linkedin.com/in/maria-rocchi-9aa7b4162/
02:4533 days ago
In vitro predictive models of particle-induced granulomas
Conferences abstracts

In vitro predictive models of particle-induced granulomas

Léa Hiéronimus is a PhD student at the Louvain centre for Toxicology and Applied Pharmacology (LTAP, UCLouvain, Belgium). Léa is working in François Huaux's team, where we are trying to better understand how certain inhaled particles exert their toxicity. The goal is to better diagnose and treat individuals exposed to particles, but also to identify the particle characteristics which induce, or do not induce, toxic effects. For this, Léa studies a very particular cell type which seems to be involved in particle responses. Indeed, we have found the specific accumulation of the innate subset of B-lymphocytes called “B-1 lymphocytes”, which occurred during granuloma formation/maturation induced by inhaled particles in mice. According to the literature, this accumulation can be attributed to their migration from mesothelial cavities such as the peritoneum, acting as a reservoir. In addition to conventional particles-induced granulomas, which formation rely on macrophages responses, we developed new models relying on B-1 lymphocytes. Indeed, B-1 lymphocytes show a unique clustering property, that is not observed using macrophages or other subsets of B-lymphocytes (conventional B-2 lymphocytes) as purified B-1 lymphocytes regroup granuloma-inducing particles (carbon nanotubes CNT7, crocidolite asbestos, micrometric silica MinUSil and MSS, cobalt oxide,…) but not carbon black, a particle not-inducing granuloma in vivo. Additionally, we developed a model aiming to recapitulate the lung after B-1 lymphocytes migration and found that macrophages and epithelial cells (MHS and LA4 cell lines) where grouped to form spheroids when in coculture with B-1 and not B-2 lymphocytes. These models will serve as tools to identify new mediators of granuloma formation, which could serve as biomarkers and/or therapeutic targets for exposed individuals. On the other hand, we aim to propose new bioassays for the prediction of granuloma-inducing materials using alternative models. Lab website: https://uclouvain.be/en/research-institutes/irec/ltap Contact: lea.hieronimus@uclouvain.be
03:1135 days ago
A phytochemical assessment of the antioxidant and cytotoxic properties  of Helleborus odorus subsp. cyclophyllus extract
Conferences abstracts

A phytochemical assessment of the antioxidant and cytotoxic properties of Helleborus odorus subsp. cyclophyllus extract

Helleborus sp. is a member of the Ranunculaceae family, and are small, perennial herbs common in Central and Southern Europe and Asia. Their distribution in Europe elevated their position in therapeutic remedies since the ancient time and mythology. Due to their potent and rich extracts from their roots, hellebores have been used in traditional and folklore remedies as they present rich sources in glycosides. Mainly, these plants have exhibited cathartic, anthelmintic and other beneficial aspects to treat diseases, however, hellebores have also been known for their adverse and poisonous aspects. It is also because of their cytotoxic aspect that these species have also been explored as alternative approaches to cancer treatment and are mainly reported as sporadic patient cases in literature. In this study, we first focused on the phytochemical characterisation of Helleborus odorus subsp. cyclophyllus combining biochemical assays and a detailed characterisation of its antioxidant and antibacterial properties. Furthermore, regarding its toxic potential, we explored the cytotoxic toxic properties and the mechanisms of toxicity mediated effects using in vitro cell systems primary human aortic endothelial cells (HAECs). HAECs are useful for studying vascular diseases such as thrombosis, atherosclerosis, and hypertension as well as for stent-graft compatibility testing and within the 3Rs principles, avoiding animals in these studies. Results showed the cytotoxic and reactive oxygen species potential of Helleborus extract in dose and time dependent manner. Further investigation (not shown here) revealed more mechanistic effects relevant to inhibition of proliferation. Contact: https://www.researchgate.net/profile/Anna-Michalaki
03:3935 days ago