New methods for vascular research reduce number of experimental animals / Human umbilical cord cells mimic vessel walls
Professor Thomas Korff of the Department of Physiology and Pathophysiology at Heidelberg University, Germany, was awarded the German Research Foundation (DFG)’s Ursula M. Händel Animal Welfare Prize on March 20, 2014, at a ceremony in Berlin.
The physiologist investigates the formation and remodeling of blood vessels and has developed methods that minimize the distress experienced by animals and reduce the number of test animals. In certain areas, animal experiments can be replaced completely.
Professor Korff plans to use the prize money in the amount of 100,000 euros to refine his methods and standardize them so that they can be introduced and applied in other research laboratories without a great deal of effort.
Blood vessels in the petri dish
The award winner and his group study the processes and mechanisms in blood vessels that underlie normal development as well as pathological remodeling processes associated with, e.g. atherosclerosis or varicose veins. In order to use human cells for his experiments to the greatest extent possible, Korff has developed special culture methods.
To this end, he cultivates spherical cellular aggregates from cells that are isolated from the blood vessels of human umbilical cord after birth. These cell masses mimic two layers of the vessel wall.
This model system for human blood vessels is not only well suited for basic research, but is now also being used in industrial applications. Scientists from Beiersdorf AG in Hamburg, Germany, are using the model system to test the protective effect of cosmetic substances on microscopic skin vessels. “Since we categorically excludeanimal testing, we use these kinds of realistic methods with human cells, which are especially significant for us,” said Dr. GittaNeufang, Head of Medical Management at Beiersdorf AG.
Test mice affected as little as possible
“However, cell cultures reach their limits for applications beyond cosmetics, for instance, if we want to find out how and why vessels undergo pathological changes,” Korff pointed out. In this case, it is not possible to avoid direct manipulations on animals, he clarified. “However, we have developed new surgical techniques that are much less stressful for the test animal than other proceduresused in vascular research.”
The new methods are easy to perform and mean less distress for the animals. “The animals behave normally and the success rate of the surgical procedures is higher. We need fewer animals for reliable results, which also reduces the costs,” he added.
For experiments on the living organism, the team often uses the ear of the mouse, in which the blood vessels are already clearly visible with the naked eye. The mouse ear is also easily accessible for many imaging techniquesand is suitable as a model for investigating many research questions. Without a single incision, for instance, a vein can be tied off in order to raise blood pressure in the afferent vessels.
In so doing, the formation of varicose veins can be simulated and their development observed over a period of several days. With this model, Korff investigates what signal pathways and molecules promote the pathological enlargement of the veins and whether certain substances can influence it. These kinds of studies are essential for identifying approaches for future therapeutic treatment.
In another project, the research group uses the mouse ear to investigate how tumors influence existing vessels or stimulate the formation of new vessels and, in so doing, can ensure their own blood supply. “Processes that are so complex can only be studied in live animals,” Korff explained.
Stretch-induced activation of the transcription factor activator protein-1 controls monocyte chemoattractant protein-1 expression during arteriogenesis. Demicheva E, Hecker M, Korff T. Circ Res. 2008 Aug 29;103(5):477-84.
Feldner A, Otto H, Rewerk S, Hecker M, Korff T. Experimental hypertension triggers varicosis-like maladaptive venous remodeling through activator protein-1. FASEB J. 2011 Oct;25(10):3613-21.
Navid F, Kolbe L, Stäb F, Korff T, Neufang G. UV-radiation induces the release of angiopoietin-2 from dermal microvascular endothelial cells. ExpDermatol. 2012 Feb;21(2):147-53.
More information is available on the Web:
Working group Professor Thomas Korff: http://www.medizinische-fakultaet-hd.uni-heidelberg.de/Gruppe-Korff.110926.0.htm...
Ursula M. Händel Animal Welfare Prize: www.dfg.de/haendel-preis
DFG press release: www.dfg.de/service/presse/pressemitteilungen/2014/pressemitteilung_nr_04/index.html
Contact for journalists:
Dr. Gerd König
Institute of Physiology and Pathophysiology
Division of Cardiovascular Physiology
Tel. +49 6221 54-4067 or +49 1525 3502007
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Heidelberg University Hospital is one of the largest and most prestigious medical centers in Germany. The Medical Faculty of Heidelberg University belongs to the internationally most renowned biomedical research institutions in Europe. Both institutions have the common goal of developing new therapies and implementing them rapidly for patients. With about 11,000 employees, training and qualification is an important issue. Every year, around 118,000 patients are treated on an inpatient basis and around 1.000.000 cases on an outpatient basis in more than 50 clinics and departments with 2,200 beds. Currently, about 3,500 future physicians are studying in Heidelberg; the reform Heidelberg Curriculum Medicinale (HeiCuMed) is one of the top medical training programs in Germany.
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