Discordant cellular and organ transplantation from bench to bedside

Abstract

It is more than 1 year since our Consortium commenced. The following abstracts provide an account of what has been achieved so far and document our understanding of xenotransplantation and some of our future strategies: Since (microencapsulated) islets are the first in the clinic, our basic research focuses on immediate (innate) rejection reactions and means of counteracting them. Once transplanted and working, porcine and primate islets may respond differently, for example to glucose challenges. We will gain preclinical experience regarding the safety of genetically modified islets as quickly as possible. We are currently in dialogue with German authorities (Paul‐Ehrlich‐Institution as representative of the European Medicines Agency) to decide how best to formulate a successful clinical application within European standards. Are there any ethical objections from within German society? A recent 3‐day meeting, held at the Munich Catholic Academy explored the issues, including opinions from the Jewish and Islamic communities. In brief, the outcome revealed no major objections as long as xenogeneic procedures are safe and effective. All talks will be published in German, with abstracts in English. There will also be an English review of the meeting possibly published in the journal Xenotransplantation. Successful preclinical organ (heart, kidney) xenotransplantation is still difficult to achieve. Heterotopic thoracic (working) heart transplantation has been established with consistent results. It seems that hyperacute and delayed humoral rejection reactions are manageable; but thrombotic microangiopathy currently presents the main obstacle. Porcine hearts that express human thrombomodulin will be used next, together with complement antibodies and/or co‐stimulation blockade. Human thrombomodulin has provided promising results in the laboratory (cell based). Porcine heart valves will be tested using single and multiple antigen knock out. In conclusion, the German Xenotransplantation Consortium supported by the German Research Foundation (DFG) is on track for a successful (first?) period. There seems to be broad support from a majority of German cardiovascular surgeons, and this is spreading to those in other parts of Europe [1].Reference[1] Reichart B., Guethoff S., Mayr T. et al. Discordant cardiac xenotransplantation – broadening the horizons. Eur J Cardiothorac Surg 2013; Epub ahead of print.