3Rs-Innovation Projects
supported by the Department Animal Welfare of the Brussels Region (former Kabinet Debaets, current cabinet Clerfayt)
Doctoral Theses
Running PhD thesis: Alexandra Gatzios
Partly sponsoring for 1 year: 2021: Development and application of a human stem cell-based in vitro model for studying NASH-fibrosis
Metabolic-associated fatty liver disease (MAFLD) is one of the most prevalent chronic liver diseases worldwide. MAFLD encompasses multiple disease stadia, ranging from benign liver steatosis to non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis and cancer. NASH often associates with liver fibrosis and is hence the tipping point to the life-threatening stages of MAFLD. Yet, no drugs against it are approved. This is partly due to a lack of suitable preclinical models. Animal models are not predictive and relevant for the human situation. Therefore, the prime objective of this research is to develop an in vitro human stem cell-based model that allows the investigation of NASH-related liver fibrosis. The project is supervised by Dr. Joost Bockmans.
Completed and partly sponsored PhD thesis: 2017-2020: Joost Boeckmans
Development and characterization of a human stem cell-based in vitro model for anti-NASH drug testing
Non-alcoholic steatohepatitis (NASH) is a severe chronic liver disease that affects about 5% of the population. NASH is characterized by hepatic lipid accumulation, inflammation and fibrosis and can progress to cirrhosis and hepatocellular carcinoma. There are currently no drugs available to treat NASH. Investigation of NASH traditionally relies on animal models, which are often not representative for the human situation. Therefore, the aim of the doctoral thesis was to develop a human-based in vitro model that can recapitulate the molecular and cellular mechanisms that drive NASH and can be used during anti-NASH drug development. The project was supervised by Prof. Robim M Rodrigues, Prof. Tamara Vanhaecke, Prof. Vera Rogiers and Prof. Joery De Kock from the Vrije Universiteit Brussel.
Completed and partly sponsored PhD thesis 2017-2020: Alessandra Natale
Shift from 2D to 3D in the development of a human skin cell-derived hepatic in vitro model for toxicological applications
Drug-induced liver injury (DILI) is a major threat to human health and is, together with absence of clinical efficiency, at the basis of a 90% failure rate in drug development. As preclinical data obtained using experimental animals do not adequately represent the human situation, in vitro models based on human cells are highly needed. In this doctoral thesis, the relevance of human-skin derived stem cells differentiated towards hepatic cells (hSKP-HPC) for toxicological screening was highlighted and the biological importance of ‘in vivo-like’ conditions for culturing and differentiating human stem cells was emphasized. Although the process requires further optimization, the results pave the way to enhance hepatic maturation which is a prerequisite to reliably predict human-specific hepatotoxicity of new pharmaceuticals. The project was supervised by Prof. Robim M Rodrigues, Prof. Tamara Vanhaecke, Prof. Vera Rogiers and Prof. Joery De Kock from the Vrije Universiteit Brussel.
in collaboration with Sciensano funded by the Departments Animal Welfare of the Flemish region (Department ‘Omgeving’) and Brussels region (former Kabinet Debaets, current cabinet Clerfayt)
The RE-Place database
This open access databaseis available for different stakeholders such as the scientific community, the government, regulators, ethical committees and other interested parties. It provides a reliable overview of the available knowledge on NAMs, but also the names of experts who you can contact and research centres where these techniques can be learned in Belgium.
WE NEED YOUR HELP
In order to obtain such an up-to-date and reliable inventory, we need the help of the scientific community in Belgium. We invite you to submit your knowledge on the NAMs in which you have experience via the RE-Place online tool (www.RE-Place.be). These methods do not necessarily have to be developed by yourself, nor by the organization you are working for. Your personal know-how on NAMs is the essential information we are looking for.
WHAT’S IN IT FOR YOU?
By submitting your expertise, you and your organisation can demonstrate your commitment to animal-free innovation and you have many different advantages:
- Increasing the visibility of your work to other scientists,
- Facilitating the search to be identified as an expert in the field,
- Exchanging experiences on the use of NAMs, learning from others and fostering new collaborations,
- Allowing the identification of knowledge gaps which will help to better allocate future funding,
- And so much more!
WHICH NAMS DOES RE-PLACE COLLECT?
We are collecting information on all NAMs in basic and applied research that avoid the direct use of animals, used as stand-alone or combined with animal experimentation to collect the information of interest. NAMs are thus not necessarily one-by-one replacement methods but can contribute to the overall replacement or reduction of animal testing. They can also be a single step within a broader research strategy.
NAMs thus include different types of:
- In vitro and ex vivo methods (e.g. experiments with the use of 2D - 3D cell lines and tissue cultures, NRU Phototoxicity Test, AMES, BCOP, …);
- In silico modeling (e.g. molecular modeling and mathematical approaches, PBPK models, QSAR, read across, …);
- In chemico techniques (e.g. assays evaluating the reactivity and properties of substances or components);
- Alternative in vivo models (e.g. fruit flies, flatworms, early stages of zebrafish, …);
- Other innovative techniques (e.g. organ-on-a-chip);
- …
DO YOU HAVE ANY QUESTIONS OR NEED HELP?
The RE-Place project is coordinated by the Vrije Universiteit Brussel and Sciensano. More information via the website www.RE-Place.be and on our YouTube Channel.
Do not hesitate to contact info@RE-Place.be or mieke.vanmulders@sciensano.be if you have questions.
in collaboration with Sciensano funded by the Flemish region (Department ‘Omgeving’)
GENOMARK II project
Evaluation of the genotoxic potential of additional compounds with GENOMARK biomarker to finalize pre-submission dossier for EURL ECVAM (2021-2022).
More coming soon.
