A research association led by the MHH is developing chip-based replacement and supplementary methods to avoid animal experiments. To this end, it is receiving 3.6 million euros in follow-up funding.
Developing replacement and supplementary methods for animal experiments and thus avoiding animal testing is the goal of the "Micro-Replace Systems" research network led by André Bleich, Director of the Institute of Laboratory Animal Science at Hannover Medical School (MHH), and Maren von Köckritz-Blickwede from the Foundation of the University of Veterinary Medicine Hannover. In 2017, the project started under the name "R2N - Replace and Reduce from Lower Saxony" with support from the Lower Saxony Ministry of Science and Culture (MWK). This primarily involved research into methods that replace experiments on living animals with studies on organ models and research on cell cultures. The research network now initiated from R2N consists of twelve working groups from the MHH, the University of Veterinary Medicine Hannover and the Technical University of Braunschweig and will receive follow-up funding of 3.6 million euros from the MWK for a further three years. In addition, a website has been set up, the 3R Portal. It informs with exciting interviews, factsheets and info-graphics about the current state of research to avoid, reduce and improve animal experiments.
Stem cells grow into mini organs
The network is primarily concerned with reducing animal testing in basic research. "It is precisely there that the number of animal experiments has been constant for years, while they are declining in other research areas," explains Professor Bleich. However, interdisciplinary collaboration has already enabled various alternative models to be developed for use in biomedical research. "These systems are also already being used, for example in COVID-19 research," says the scientist.
The main areas of research in the first funding period were, for example, the non-animal safety assessment of gene therapies or transplants from other species, the digestive tract - especially the oral mucosa, intestine and liver - and the upper and lower respiratory tract. Here, research with adult and induced pluripotent stem cells (iPSC) was particularly developed. iPSC are biotechnologically "reprogrammed" cells with the property of being able to divide indefinitely and develop into any desired body cell. So-called organoid systems have been developed based on stem cells. Applied to a special chip, the cells can be used to form the smallest organs and supplied with nutrients via tiny tubes and channels. The researchers have used intestinal stem cells to grow mini intestines, for example, which can be used for scientific studies.
Chip systems: sustainable and reusable
Now the researchers want to develop a new, standardized chip system on which they can observe the interaction between intestinal or respiratory cells and immune cells. To replicate the system as faithfully as possible, the culture conditions must also be adapted. "This is because, for example, the oxygen conditions in the intestine are different from those in the lung tissue in the breath," says Professor von Köckritz-Blickwede. "It’s important that we can perform the studies under realistic conditions and transfer them as best as possible to reality, such as in the case of an infection." Tailored according to tissue type, the corresponding living conditions and the respective scientific question, the chip systems should be versatile and also reusable. Furthermore, a newly developed bio membrane permeated by blood vessels will ensure that the various tissues can grow better and allow more extensive investigations. Special non-animal antibodies will be developed and used for the research questions. In an overarching project, the new systems will then be subjected to intensive quality controls to ensure that they are as transferable as possible for widespread use.
However, the chip systems will not only be equipped with human stem cells. The researchers also want to replicate animal models. "Many very fundamental investigations in basic research are carried out on mouse models," explains Professor Bleich. "Especially in this area, we could avoid many experiments on living animals with our chip systems."