hOrganoid for animal-free food hazard identification analysis

hOrganoid for animal-free food hazard identification analysis

Aantal projecten

1

Organisatie onderdeel

WR-cap AF

Project code

LWV19125

Primaire MMIP

Landbouw, Water, Voedsel>D. Gewaardeerd, gezond en veilig voedsel>D4. Duurzame en veilige verwerking

Start datum

01/01/20

Eind datum

31/12/23

Samenvatting

The project aims to develop human intestinal organoids and to apply these in the area of (agri)food & health for animal-free research on hazard identification. Our current in-house methods for organoid culturing will be optimized to ascertain a robust screening method and the performance of the system under dynamic flow conditions will be tested in organ-on-chip devices. Next we aim to identify relevant ‘show cases’ to evaluate the predictive capacity of the model using chemicals, for which in vivo data are available and use a comparative analysis approach to validate the human organoid assay as a predictive model for hazard identification analyses of new and existing compounds intended for human intake as well as of (emerging) contaminants in the food chain.

Doel van het project

The project will support safe innovation and contribute to animal-free safety assessment.
Innovation will lead to new or recycling compounds that can enter the food system and should be analysed for potential adverse effects on human health. These safety evaluations still depend on animal studies. Besides not being fully predictive for humans, animal experiments encounter many objections from society. As alternative methods for animal models, a large variety of human based in vitro methods has been developed during the last decades, but they often fall short on certain aspects, leading to testing approaches where animal testing is still the standard in toxicology testing. It has been demonstrated that novel model systems like organoids have a composition that is more similar to the real-life situation and are thus predicted to have a better prediction capacity. The application of this project therefore supports the required innovation in the agriculture, water and food sector. In addition, a clear mission of the Dutch government is to work towards reduction and ultimately elimination of animal testing, which is also supported by this project.

Relatie met missie (Motivatie)

Animal models are still the golden standard to evaluate potential food hazards. However, their relevance is disputed as species extrapolation has often proven to be inaccurate leading to mispredictions for humans. Moreover, the Dutch government works towards a reduction and ultimately elimination of animal testing. As alternative methods for animal models, human based in vitro models have been developed, but they are often oversimplified consisting of only a single cell type to represent the entire organ. Due to these limitations current in vitro models are often not fully predictive for humans, indicating a clear need for in vitro models with a better prediction capacity towards in vivo outcomes for food hazard identification studies.
Novel model systems like organoids comprise a higher cellular complexity that is more similar to the real-life situation and are predicted to achieve a more reliable prediction of potential hazards for human health. The application of this project therefore supports the required innovation in the agriculture, water & food sector.

Geplande acties

1. Develop reproducible human 2D and 3D intestinal organoid protocols
Deliverable 1.1 Set up protocols for the generation of intestinal organoids derived from human induced pluripotent stem cells (iPSCs) or from intestinal adult stem cells obtained from biopsies/chirurgery waste material. Various culturing parameters and culture media and/or growth factor compositions will be tested and optimized. (month 1-24)
Deliverable 1.2 Characterize the tissue make up and development/differentiation of both systems compared to human primary tissue. Especially, the effect of cell culture media composition will be studied as well as the stability of organoids during culture passaging, and the reproducibility over a longer time frame, or when derived from different location in the intestine or from different individuals will be studied. (month 1-24)
Deliverable 1.3 Set up protocols to grow 2D intestinal organoids in organ-on-chip platforms. For integration into the chip devices one type of organoid (i.e. derived from adult stem cells or iPSCs) will be selected based on the results from Task 1.1 and 1.2. The influence of a fluid flow on the tissue characteristics will be evaluated as described in Task 1.2. (month 6-36)

2 Select and test compounds based on available in vivo
Deliverable 2.1 Create an overview (database) of compounds with relevant data from available in vivo studies and select appropriate readouts to analyze responses from organoids to align with these data. (month 1-6)
Deliverable 2.2 Study the responses of compounds and chemicals for which in vivo data are available (like data obtained from toxicity studies in animals from previous research available from the partner companies or obtained from literature and public databases). (month 12-48)

3 Enhanced data analysis, extrapolation and predictive modelling
Deliverable 3.1. Bioinformatics and pathway based approaches to compare the responses from organoids and the in vivo data to assess whether conclusions drawn related to adverse effects are in line with the different models. When in vivo human data are available we will evaluate whether the human organoid models provide better predictions for humans than the animal models. (month 24-48)
Deliverable 3.2. Study new chemicals, compounds and products of interest for partner companies based on the developed and validated methods. (month 36-48)

4 Interaction with food authorities on model validation and acceptance requirements
Deliverable 4.1. Discuss the progress and raise awareness for the possibilities to use organoid models as alternative methods for hazard identification studies in the food domain with regulators from food authorities (i.e. EFSA) and EU Reference Laboratory for alternatives to animal testing (EURL-ECVAM). (month 6-48)

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