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Immune Responses to Biosurfaces pp 143–155Cite as

Xenotransplantation of Cells, Tissues, Organs and the German Research Foundation Transregio Collaborative Research Centre 127

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 865))

Abstract

Human organ transplantation is the therapy of choice for end-stage organ failure. However, the demand for organs far exceeds the donation rate, and many patients die while waiting for a donor. Clinical xenotransplantation using discordant species, particularly pigs, offers a possible solution to this critical shortfall. Xenotransplantation can also increase the availability of cells, such as neurons, and tissues such as cornea, insulin producing pancreatic islets and heart valves. However, the immunological barriers and biochemical disparities between pigs and primates (human) lead to rejection reactions despite the use of common immunosuppressive drugs. These result in graft vessel destruction, haemorrhage, oedema, thrombus formation, and transplant loss. Our consortium is pursuing a broad range of strategies to overcome these obstacles. These include genetic modification of the donor animals to knock out genes responsible for xenoreactive surface epitopes and to express multiple xenoprotective molecules such as the human complement regulators CD46, 55, 59, thrombomodulin and others. We are using (new) drugs including complement inhibitors (e.g. to inhibit C3 binding), anti-CD20, 40, 40L, and also employing physical protection methods such as macro-encapsulation of pancreatic islets. Regarding safety, a major objective is to assure that possible infections are not transmitted to recipients. While the aims are ambitious, recent successes in preclinical studies suggest that xenotransplantation is soon to become a clinical reality.

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Funding

The Transregio Collaborative Research Center 127 is funded by the German Research Foundation (DFG).

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Authors and Affiliations

  1. Walter Brendel Centre of Experimental Medicine, Ludwig-Maximilians-Universität (LMU), Munich, Germany

    Bruno Reichart, Sonja Guethoff & Tanja Mayr

  2. Department of Cardiac Surgery, LMU, Munich, Germany

    Paolo Brenner & Thomas Poettinger

  3. Molecular Animal Breeding and Biotechnology, Gene Center, LMU, Munich, Germany

    Eckhard Wolf (Chair)

  4. Department of Medicine III, Technical University, Dresden, Germany

    Barbara Ludwig

  5. Livestock Biotechnology, Technical University, Munich, Germany

    Alexander Kind

  6. Department of Anaesthesiology, LMU, Munich, Germany

    Jan-Michael Abicht

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  1. Bruno Reichart
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  2. Sonja Guethoff
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  4. Thomas Poettinger
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  5. Eckhard Wolf
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  6. Barbara Ludwig
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  8. Tanja Mayr
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  9. Jan-Michael Abicht
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Correspondence to Bruno Reichart .

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Editors and Affiliations

  1. Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA

    John D. Lambris

  2. Immunology, Genetics and Pathology, University of Uppsala, Uppsala, Sweden

    Kristina N. Ekdahl

  3. Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA

    Daniel Ricklin

  4. Immunology, Genetics and Pathology, University of Uppsala, Uppsala, Sweden

    Bo Nilsson

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Reichart, B. et al. (2015). Xenotransplantation of Cells, Tissues, Organs and the German Research Foundation Transregio Collaborative Research Centre 127. In: Lambris, J., Ekdahl, K., Ricklin, D., Nilsson, B. (eds) Immune Responses to Biosurfaces. Advances in Experimental Medicine and Biology, vol 865. Springer, Cham. https://doi.org/10.1007/978-3-319-18603-0_9

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