Project Group “White Paper - Animal Research in the Max Planck Society”

The project group "White paper - animal research in the Max Planck Society" is developing brain organoids based on iPS cells as an alternative to animal experiments. The iPS cell technology provides for the first time the possibility to establish innovative in vitro models for neurodegenerative diseases in the human system, which not only have the great potential to significantly contribute to the reduction of animal experiments in neuroscience, but also to sustainably promote the quality of science.

Animal research has long been a valuable tool for elucidating the mechanisms of human disease. However, neurological disorders such as Alzheimer's and Parkinson's have proven extremely difficult to model in animals. Reasons for this are that the human brain is more complex and also that these diseases often do not occur naturally in mice.

As alternatives to animal experiments, single-layer growing cells in 2D cell cultures are often used as in vitro models for patho-/physiological questions. The ease of handling, high growth rate, and morphological and metabolic homogeneity of these cells make them attractive as model organisms. However, these cells exhibit numerous alterations compared to native tissue cells, which therefore do not always lead to reliable conclusions about physiological relevance in native tissue.

Organoids bridge the gap between classical 2D cell cultures and in vivo mouse models because they are physiologically more relevant than 2D cultures and are by far more accessible for studies of cellular signaling pathways. The use of induced pluripotent stem (iPS) cells ensures the almost unlimited availability of human starting material for organoid establishment.

So, in order to represent diseases as well as possible in the culture dish, scientists have been using three-dimensional, rather than two-dimensional, culture systems for several years, because 3D systems are much closer to cellular diversity and its complex structure and interactions in organs. Organoids are a kind of 3D culture system. They grow and mature in a self-organizing manner from iPS cells or tissue-specific progenitor cells into a tissue aggregate, just as would happen in the human body. Because the cells in organoids self-organize, organoids are more complex, better mimic the characteristic physiological properties of tissue, and therefore offer several functional advantages over traditional models.

By combining the power of iPS reprogramming technology with emerging 3D cell culture technology, researchers are able to generate patient-specific tissues that not only allow them to study the cause and treatment of neurodegenerative diseases in native human tissues (without ethical issues), but also open the door to personalized medicine.

Organoids - even if they cannot completely replace animal research - have great potential not only in basic biological/medical research. They will also help to reduce animal testing in the areas of drug efficacy testing, drug safety testing and in toxicological testing.

Reduce, Improve, Avoid - Responsibility

Organoid research is therefore in line with the Max Planck Society Declaration of Principle on Animal Research. In this statement, the scientists in the Max Planck Society commit themselves to keeping the number of animal experiments as well as the stress on the animals in the individual experiments as low as possible. In planning and conducting the experiments, they apply the so-called 3R principle. 3R stands for "reduce, refine, replace": The number of animals per experiment is reduced to the absolute minimum (reduction); the conduct of the experiments and the husbandry of the animals are optimized in such a way that the stress on the animals is kept as low as possible (refinement); animal experiments are replaced by alternative methods (for example cell cultures, computer models, imaging techniques) whenever possible (replacement).

In addition, the researchers of the Max Planck Society commit to an "R" for "Responsibility" or accountability (4R principle) in their 2016 policy statement. They want to use their knowledge in the life sciences and humanities to promote animal welfare in their institutes.


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