title: Xenotransplantation of Cells, Tissues, Organs and the German Research Foundation Transregio Collaborative Research Centre 127.
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.
authors: Walter Brendel Centre of Experimental Medicine, Ludwig-Maximilians-Universität (LMU), Munich, Germany, Bruno.Reichart@med.uni-muenchen.de.
authors: Bruno
authors: B
authors: Reichart
authors: Sonja
authors: S
authors: Guethoff
authors: Paolo
authors: P
authors: Brenner
authors: Thomas
authors: T
authors: Poettinger
authors: Eckhard
authors: E
authors: Wolf
authors: Barbara
authors: B
authors: Ludwig
authors: Alexander
authors: A
authors: Kind
authors: Tanja
authors: T
authors: Mayr
authors: Jan-Michael
authors: JM
authors: Abicht
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D035843:Biomedical Research / Q000379:methods / Q000639:trends; D051056:Complement Inactivating Agents / Q000627:therapeutic use; D005582:Foundations; D015870:Gene Expression / Q000276:immunology; D005858:Germany; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D016027:Heart Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016381:Islets of Langerhans Transplantation / Q000276:immunology / Q000379:methods*; D013552:Swine; D018180:Thrombomodulin / Q000235:genetics / Q000276:immunology; D019076:Transgenes; D014183:Transplantation, Heterologous
chemical_list: D015703:Antigens, CD; D051056:Complement Inactivating Agents; D007166:Immunosuppressive Agents; C546931:THBD protein, human; D018180:Thrombomodulin