Xenotransplantation

Xenotransplantation refers to the transplantation of functioning cells, tissue or organs between different species in general, and more specifically to animal-to-human transplantation. This term is in contrast to allogeneic transplantation (transplantation where donor and recipient belong to the same species). First attempts to replace human organs with animal organs were made as early as in the beginning of the 20th century. The first successful xenotransplantation was finally performed in 1963 when the surgeon Keith Reemtsma transplanted kidneys from chimpanzees into six patients; however, none of these kidneys continued to function for more than nine months. Since 1990, there has been an increasing number of transplantations of pig cells and tissues. Due to their anatomical and physiological characteristics, pigs are particularly suitable donors, since their organs are similar to human organs in size and function; moreover, the husbandry and breeding of pigs is relatively easy. Pig brain cells are used in the treatment of Parkinson’s disease, pig islet cells are used to treat diabetes, and pig liver cells are transplanted into human patients with liver failure. 

However, like any experimental therapy, xenotransplantation involves a number of problems and risks. Due to the phylogenetic distance between humans and animals, the transplanted material is usually rejected more rapidly and more violently than is the case with allogeneic transplants. The immunosuppressive agents which are available at present do not yet allow to suppress xenograft rejection in the long term. There are attempts to increase the chances of success of xenotransplantations by targeted genetic modification, e.g. of the tissue factors of pigs. Nonetheless, it is still uncertain whether pig organs and other animal transplants can reliably substitute for the functions of human organs in the long term. Among other things, the upright posture of man could have an unforeseeable effect on the transplanted pig organs.

In May 2022, a team of researchers published a study in which two brain-dead people were transplanted pig kidneys together with tissue parts of the thymus. The thymus is an organ that produces immune cells, and it was hoped that transplanting it would improve acceptance of the transplanted pig kidneys. The pigs had also been genetically modified to prevent rejection reactions. For this purpose, a gene was deactivated that produces a specific protein (alpha-1,3-galactosyltransferase) that causes rejection reactions in humans. The study period was 54 hours, during which time the kidneys functioned normally and no rejection reactions were observed. A few months earlier, another research team had also transplanted kidneys from a genetically engineered pig into a brain-dead human. In this case, too, no rejection reactions were observed over the study period of 74 hours, but kidney function was impaired.

Some researchers are critical of the two studies. Regarding the first study, it was objected that the study results were problematic because the "thymus kidneys" were additionally transplanted and the brain-dead patient still had his own kidneys – it could therefore not be determined with certainty whether the urine had been produced by the pig kidneys or the human kidneys. The general criticism against both studies was that the study periods had been very short and that it could not be excluded that rejection reactions would still have occurred at a later stage.

Stellungnahme des Wissenschaftlichen Beirates der Bundesärztekammer zur Xenotransplantation. Online Version (German)

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Lu, T. / Yang, B. / Wang, R. / Qin, C. (2020): Xenotransplantation: Current Status in Preclinical Research. In: Frontiers in Immunology 10, 3060. doi: 10.3389/fimmu.2019.03060. Online Version

Montgomery, R. A. et al. (2022): Results of Two Cases of Pig-to-Human Kidney Xenotransplantation. In: The New England Journal of Medicine 386 (20), 1889–1898. doi: 10.1056/NEJMoa2120238. Online Version

Porrett, P. M. et al. (2022): First clinical-grade porcine kidney xenotransplantation using a decedent human model. In: American Journal of Transplantation 22 (4), 1037–1053. doi: 10.1111/ajt.16930. Online Version

Sautermeister, J. (Hg.) (2018): Tierische Organe in menschlichen Körpern. Biomedizinische, kulturwissenschaftliche, theologische und ethische Zugänge zur Xenotransplantation. Paderborn: Mentis. (German)

Singer, P. (2001): Xenotransplantation and Speciesism. In: Kuhse, H. / Singer, P. (ed.): Bioethics: An Anthology. Oxford [u.a.]: Blackwell, 412–417.

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