He received the award for his exemplary implementation of the 3R principle (Reduction, Refinement, Replacement). Korff has developed a variety of methods that reduce the burden on the animals used in tests and the numbers of animals used, as well as providing alternatives to animal tests.

The award ceremony took place in Berlin on 20 March 2014 and was preceded by a workshop on “Animal Models in Research – Opportunities and Limitations”.

InVitroJobs interviewed the prize recipient Prof. Korff.



Image: T. Korff.


InVitroJobs:
First of all, we’d like to congratulate you on receiving the Ursula M. Händel Animal Welfare Prize.

Prof. Korff:
Thank you.

InVitroJobs:
As an animal welfare organisation we are of course especially interested in the “replacement” part of 3R, which is why we would like to ask you a few questions. First of all, can you give us a general idea of what you have been researching and what insights you have gained?

Prof. Korff:
We research biomechanically induced mechanisms that either promote pathological changes in the vascular system or can at least partially compensate their harmful effects. Amongst other things we are interested in the genesis of arteriosclerotic damage and the transformation of arteries, such as is caused by hypertension. Our field of study includes angiogenesis (i.e., the creation of new blood vessels) caused by tumour growth. We characterise proteins that govern the behaviour of smooth muscle cells in the walls of the blood vessels. Thus we could for instance identify mechanisms responsible for the alteration of arterial walls in the case of hypertension.

InVitroJobs:
What kind of cell culture did you use, and how important was the cell culture?

Prof. Korff:
We have developed a method for cultivating human endothelial cells and smooth vascular muscle cells together in three-dimensional aggregates. We obtain the cells from the blood vessels of umbilical cords after birth. The 3D cell cultures have much better characteristics than conventional 2D cultures and are more similar to the conditions in organisms. Cells in 2D culture proliferate, and that kind of growth doesn’t normally take place in an adult body. These proliferating cells are usually hard to activate, so they don’t synthesise the proteins the way tissue does and don’t behave normally. That is why I started cultivating cells in 3D almost twenty years ago. You can use them to perform many experiments that can’t be conducted in 2D cultures. If I let the cells grow in a collagen gel as round aggregates, so-called spheroids, after a while small vessels sprout outwards into the gel. I can use this structure for testing substances that can inhibit or promote angiogenesis. Bortezomib is such a pharmaceutical drug that has been approved for treating multiple myeloma and suppresses vessel growth in our cultures.

We have also made the model available to other scientific institutes, including for training and qualification, for instance Promocell in Heidelberg. Many groups now test a variety of active agents with the help of the spheroids.

Another model we have developed is based on the outer ears of mice. Instead of administering the substance systemically and observing its effect in the animal based on initial insights gained in vitro, we can apply the substance – which would otherwise be distributed throughout the whole body and is rather aggressive - locally to the ear. This is much less stressful to the animal than the conventional method, which causes many test animals to die of multiple organ failure, which means that we also do not need so many animals. The effect of the test substance on the vascular system can also be investigated much more gently and non-invasively with the ear, for instance using modern imaging techniques or by investigating the blood flow in the tissue with modern ultrasound devices.

InVitroJobs:
Do you think that the use of cell cultures has become an indispensible aspect for your research?

Prof. Korff:
Definitely. We use the human-specific cell culture model for screening substances. The advantage is that this already gives us an idea of the dose that would most likely be effective in humans, which allows us to greatly reduce the number of animals used in the subsequent test series.

InVitroJobs:
Why couldn’t you research the other questions without using animals?

Prof. Korff:
Despite all the progress made in tissue engineering, you can only answer fundamental questions regarding the interaction of several cell types or changes in entire organ systems using the organism itself.

For instance, arteriosclerosis research without the use of any animals will still not be possible in the future. The field of research is so complex that you need four to six cell types, vessels with their specific characteristics that are shaped by their highly complex non-cellular environment, a metabolism and the biomechanical influence of the pulsating blood flow. All that can’t be simulated in a culture. But of course animal tests have their limits, just like cell cultures. No animal model is 100% suited to completely depicting human conditions. If one is aware of this, one can nonetheless obtain important biomedical information relevant to humans. In order to gain maximum insights, we depend on a considered and coordinated employment of both methods: human cell cultures and gentle animal tests.

InVitroJobs:
Thank you for the interview.

Link: http://www.spherogenex.de