Hyperacute rejection in ex vivo-perfused porcine lungs transgenic for human complement regulatory proteins

Poling, Jochen and Oezkur, Mehmet and Kogge, Karina and Mengel, Michael and Niemann, Heiner and Winkler, Michael and Haverich, Axel and Wiebe, Karsten (2006) Hyperacute rejection in ex vivo-perfused porcine lungs transgenic for human complement regulatory proteins. TRANSPLANT INTERNATIONAL, 19 (3). pp. 225-232. ISSN 0934-0874, 1432-2277

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Abstract

Inhibition of complement activation via human membrane-associated complement regulators is known to prevent hyperacute rejection in heart and kidney pig-to-primate transplantation. The protective effect of such strategies in pulmonary xenografts, however, seems to be insufficient. In an ex vivo perfusion, model lungs from donor pigs transgenic for human CD55 (n = 6) or human CD59 (n = 5) were perfused with fresh human blood and compared with nontransgenic organs (n = 6). In addition, a soluble complement component 1 esterase inhibitor (C1-Inh) was applied in h-CD55 transgenic lungs (n = 3). In the h-CD55 transgenic group, survival was prolonged (P < 0.05), quality and maximal time of oxygenation significantly improved and pulmonary vascular resistance reduced compared with the control group. There was a decreased sequestration of platelets, less parenchymal injury and reduced deposition of C5b-9 in the h-CD55 transgenic group. Additional soluble complement inhibition (C1-Inh) did not prolong survival of h-CD55 transgenic lungs. Survival and pulmonary function in lungs expressing h-CD59 was not significantly different from parameters observed in nontransgenic lungs. In this ex vivo model of pig-to-primate lung transplantation, membrane-based complement inhibition resulted in significantly improved pulmonary function. However, minor histopathological injuries observed in these transgenic xenografts suggested only partial protection from pulmonary dysfunction by complement inhibition alone.

Item Type: Article
Uncontrolled Keywords: TO-HUMAN MODEL; DECAY-ACCELERATING FACTOR; PULMONARY XENOTRANSPLANTATION; SWINE LUNGS; XENOGRAFT REJECTION; PRIMATE MODEL; INJURY; TRANSPLANTATION; PERSPECTIVES; DYSFUNCTION; complement inhibition; lung perfusion; transgenic organs; xenotransplantation
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Herz-, Thorax- und herznahe Gefäßchirurgie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 22 Feb 2021 09:36
Last Modified: 22 Feb 2021 09:36
URI: https://pred.uni-regensburg.de/id/eprint/34924

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