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Pigs as Organ Donors

protected against human immune cells

Munich, 01/21/2009

The latest analysis by the German Foundation for Organ Transplantation has revealed that fewer and fewer people are donating their organs in the event of their death. Across all of Germany last year, around one thousand patients died on the waiting list, and about 12,000 people are still waiting. One possibility to compensate for this dramatic lack of donor organs could be to transplant animal tissue or organs. Pigs have so far been considered the most suitable donor organisms, but they are no exception to the difficulty of transferring any tissue between different species, where complex rejection mechanisms need to be overcome. An international group led by Professor Elisabeth Weiss of the Bio Center and Professor Eckhard Wolf of the Gene Center of LMU have now produced genetically modified pigs whose cells, for the first time ever, are protected against destruction by human natural killer cells, which are vital immunological factors.

The human immune system is supposed to protect the organism against intruders. This is why transplanted tissue is nearly always attacked to the point of complete destruction. Especially after a xenotransplantation, that is the transfer of tissue from one species to another, the result is an excessive reaction of the body’s defenses. The most abundant actors in such a reaction are the natural killer cells – or NK cells – that quickly and efficiently eliminate foreign or infected cells.

Enormous effort is being made by research groups around the world to turn pigs into suitable organ donors by targeted modification of their DNA. An international group led by Professor Elisabeth Weiss and Eckhard Wolf has now managed to produce genetically modified pigs whose cells are protected against destruction by natural killer cells. The activity of these immune cells is controlled by receptors on their surface.

Healthy cells of an organism’s own body, for example, carry so-called MHC class I molecules on their surface, which in turn bind to inhibiting receptors on the NK cells. The result: activation of the defense cells is suppressed, and the healthy body cells are not attacked. On the surface of pig cells are also MHC class I molecules, but they are not the same as ours, so they cannot bind to the inhibiting receptors on human NK cells, and are destroyed as a consequence.

The genetically modified pigs, on the other hand, carry the human MHC class I molecule HLA-E on their surface. “We cultivated these cells together with activated human NK cells,” reports Weiss. “The majority of them survived unharmed. Normal pig cells, on the other hand, were almost completely destroyed in this experiment.” Professor Bruno Reichart, Director of the Clinic of Cardiac Surgery of LMU Medical Center, Großhadern campus, and spokesman for the research group “Xenotransplantation” funded by the German Research Foundation (Deutsche Forschungsgemeinschaft), regards this result as an important step on the path towards transplantation of animal organs. (suwe)

Publication:
“HLA-E/Human Beta2-Microglobulin Transgenic Pigs: Protection Against Xenogeneic Human Anti-Pig Natural Killer Cell Cytotoxicity”,
Elisabeth H. Weiss, Benjamin G. Lilienfeld, Sigrid Müller, Elfriede Müller, Nadja Herbach, Barbara Keßler, Rüdiger Wanke, Reinhard Schwinzer, Jörg D. Seebach, Eckhard Wolf, and Gottfried Brem,
Transplantation, Vol. 87, No. 1, 15 January 2009

Contact:
Professor Dr. Elisabeth Weiss
Tel.: +49 (0) 89 / 2180 – 74317
Fax: +49 (0) 89 / 2180 – 74331
E-mail: Elisabeth.Weiss@lmu.de

Professor Dr. Eckhard Wolf
Tel.: +49 (0) 89 / 2180 – 76800
Fax: + 49 (0) 89 / 2180 – 76849
E-mail: ewolf@lmb.uni-muenchen.de

 

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