Organoids Ellen van den Bogaard

- Organoids of the skin

Organoids are small, simple versions of human organs made from human cells. Ellen van den Bogaard is Professor of Innovative Experimental and Translational Dermatology, and she conducts research on and with organoids of the skin. By developing small pieces of cultured skin, fewer experimental animals are needed.

"We study the biological processes in our skin, looking at specific inflammatory diseases such as eczema and psoriasis. In the lab, we mimic the skin with skin models made from human cells. This gives us new insights into how disease mechanisms work. And with that, we can look for new or adapted treatments for people with these skin diseases."

"We use a very specific type of organoid, an organotypic, for the skin models, in which we can mimic the different layers of the skin. The outside of human skin is the stratum corneum, and so it is in our model. In this way we can approach reality as closely as possible: we want to know what happens when the stratum corneum comes into contact with environmental factors, such as bacteria. Most laboratories absolutely do not want their cell and tissue cultures to come into contact with bacteria, in our case it is very important in the research. After all, the skin is our protective layer against external influences, and we want to know how that process works in disease and health."This type of research is mostly done with animal models; we do it with human skin organoids.

"There is already a lot of use of organoids, but their development is also ongoing. For example, we are working with the CRISPR-Cas technique. This makes it possible to change DNA, by making genetic modifications in cells. Now we can make small pieces of skin in which certain genes do or do not function. This allows us to unravel the actual functional consequences of genetic risk factors for disease. We have done the same for a gene involved in the development of eczema. This gene (filaggrin), which is important for the construction of the epidermis and the barrier function of the skin, we have switched off in skin cells. Using these cells, we created skin models, and possibly found new processes that could explain the risk of eczema. This type of research is mostly done with animal models; we do it with human skin organoids."

"The skin of a rodent is very different from that of humans, both in terms of hair and structure. And the bacteria commonly found in people with eczema, the Staphylococcus aureus bacteria, is not naturally found in rodents at all. With new cell culture methods, we can now expose skin organoids to bacteria and fungi. And with CRIPSR-Cas we are studying the interaction between genetic and environmental factors involved in disease. But I am also convinced that laboratory animals are very important and we may never be able to do without them completely. Complex processes in the immune system such as the development of chronic inflammation or, for example, certain itch processes that lead to scratching behaviour are difficult to model in a breeding dish."

"However, I do think that the scientific community needs to value non-animal studies differently. To what extent should you validate human culture models in animals? Years ago we investigated the effect of tar ointment, a drug that works very well against skin diseases, but is not popular because of the smell and a stigma regarding (unproven) negative side effects of the treatment. Using skin organoids, we found that the ointment activates a certain receptor in skin cells, which inhibits the production of inflammatory substances in the skin, thereby stimulating the production of building blocks that are important for the function of the skin as a barrier against the outside world. Important results, without using any animals. But the question the journal where we wanted to publish it asked was: 'Will you confirm this with research in laboratory animals?' Then we went to another reputable journal that was willing to publish it."

"This research has had a great impact within dermatology, and beyond, as the receptor is now seen and appreciated as a reliable therapeutic target. Our research has been the impetus for the development of new treatments against skin diseases by the pharmaceutical industry, and I believe that in five to ten years we may have a good alternative to tar ointment, provided the new medication will be affordable."

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Research Laboratory animal research

Responsible research with laboratory animals

Radboudumc wants to lead the way in creating sustainable, innovative and affordable health care. This starts with good scientific biomedical research. For most of our research we use laboratory studies and human volunteers, for example. However, for some biological and medical research, animal research is still indispensable or sometimes even required by law.

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Responsible research with laboratory animals

At Radboudumc, we want to be on the forefront in creating a sustainable, innovative and affordable healthcare system. Every day we strive for better care, research and education; every day we get a better understanding of how diseases arise and how we can prevent, treat and cure them. In short, we want to have a significant impact on health care: being distinctive together with and for our patients.

This starts with good scientific biomedical research. For most of our research at Radboudumc and Radboud University we use laboratory studies, cell and tissue culture techniques, computer simulations and human volunteers. For some biological and medical research, however, studies in laboratory animals are still indispensable or sometimes even required by law. When there is no alternative, we conduct studies with laboratory animals at Radboudumc. Test animals help us to acquire fundamental knowledge about how humans and animals function and give us insight into the origin and course of certain diseases. This is essential for developing new treatment methods and determining how effective they are.

Animal research is conducted only under strict conditions:

  • The research questions cannot be answered by existing scientific literature.
  • Alternative methods without the use of laboratory animals are not available.
  • Two independent committees, the Animal Research Committee (Dierexperimentencommissie (DEC)) and the Central Committee on Animal Experiments (Centrale Commissie Dierproeven (CCD)), must approve the studies.
  • Laboratory animal research is based on the 3Rs: replacement, reduction, and refinement.
  • Radboud University has the appropriate facilities, expertise and license to conduct scientific experiments with laboratory animals. The Netherlands Food and Consumer Product Safety Authority (Nederlandse Voedsel‐ en Warenautoriteit (NVWA) periodically checks whether the animal experiments are carried out according to laws and regulations.
  • Radboudumc's and Radboud University's laboratory animal research is conducted at the Animal Research Facility.

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Why research with laboratory animals?

The research helps us to develop knowledge about how humans and animals function. It also helps us learn more about how certain diseases arise and how they can be treated or cured.

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Why research with laboratory animals?

Within Radboudumc and Radboud University, both fundamental as well as (bio-)medical research is conducted. At present, not all research questions can be answered by laboratory research or research with human volunteers. This is why we also use laboratory animals for our (scientific) studies at Radboudumc.

Animal experiments are currently still an indispensable part of most of biological, medical and veterinary research. They help us to develop knowledge about how humans and animals function, and to learn more about how certain diseases arise and how they can be treated or cured.

Animal research is necessary to:

  • Obtain fundamental knowledge of biological processes that can be translated to humans and investigated further in humans.
  • Learn how diseases are caused.
  • Develop new treatment options and determine how effective they are.  
  • Develop vaccines and other methods to prevent disease.

Basic principles

When laboratory animal research is conducted, it is done responsibly. In order to do so, Radboudumc strives for the so-called 3 Rs:

  • Replacement
  • Reduction
  • Refinement
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Basic principles

When laboratory animal research is conducted, it is done responsibly. In order to do so, Radboudumc strives for the so-called 3 Rs: replacement, reduction and refinement (commissioned by the Centrale Commissie Dierproeven (Dutch) by order of the government).

During each phase, we consider whether a research question can be answered without laboratory animals (replacing), with fewer animals (reducing) or with a reduced level of distress for the animals (refining). Every day we work from these basic principles and in close collaboration with members of the animal welfare body (AWB), biotechniciansand animal caretakers.

Leading the way in reducing

As Radboudumc and Radboud University, our shared ambition is to lead the way in developing and applying techniques and models that help us reduce the number of laboratory animals used in our experiments.

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Leading the way in reducing

As Radboudumc and Radboud University, our ambition is to lead the way in developing and applying techniques and models that help us reduce the number of laboratory animals used in our experiments.

For example, we increasingly use alternatives to laboratory animals, such as computer simulations, cell models, organoids and organ-on-a-chip models derived from patients' cells. In addition, the application of molecular imaging techniques is receiving increasing attention. These are techniques in which biological processes such as cell division, gene expression, metabolism, cell migration and activity of enzymes can be studied quantitatively in a laboratory animal, non-invasively at multiple time points. This results in the use of fewer animals because more information can be obtained from one animal. Another important development is optimizing research with laboratory animals by better inventorising our current knowledge, such as by systematic reviews.

Examples of innovations without animal testing:

Animal Research Facility

Radboudumc and Radboud University laboratory animal research is conducted in the Animal Research Facility. The facility provides advice, workspace, and expertise from planning to execution.

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Committees

Animal Research Committees assess whether the importance of a study outweighs the harm to the animals. With the advice of a committee, the Central Committee on Animal Experiments determines whether someone is granted a license for animal research. The Central Committee oversees the operations.

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Legislation

Radboudumc and Radboud University not only want to comply with the applicable laws and regulations, but we also actively work on new methods and insights to improve animal welfare and reduce the use of laboratory animals.

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Legislation

The laws and regulations about animal testing have been expanded during the last decade. The legislation on animal experimentation in the Netherlands is described in the Animal Experiments Act, which is based on and goes beyond the European Directive 2010/63/EU.

Radboud University has a license to conduct scientific experiments with laboratory animals. The Dutch Food and Consumer Product Safety Authority (NVWA) regularly checks whether the animal experiments are conducted according to these laws and regulations.

Every institute licensed to conduct animal experiments annually reports on their experiments with laboratory animals. This information is collected nationally and published in the annual rapport ‘Zo Doende’, the NVWA's annual overview of animal experiments and laboratory animals. Radboud university medical center and Radboud University not only want to comply with the current laws and regulations, but we also actively work on new methods and insights to improve animal welfare and further reduce the use of laboratory animals.

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