Impact of porcine cytomegalovirus on long-term orthotopic cardiac xenotransplant survival
-
Published:2020-10-16
Issue:1
Volume:10
Page:
-
ISSN:2045-2322
-
Container-title:Scientific Reports
-
language:en
-
Short-container-title:Sci Rep
Author:
Denner Joachim,Längin Matthias,Reichart Bruno,Krüger Luise,Fiebig Uwe,Mokelke Maren,Radan Julia,Mayr Tanja,Milusev Anastasia,Luther Fabian,Sorvillo Nicoletta,Rieben Robert,Brenner Paolo,Walz Christoph,Wolf Eckhard,Roshani Berit,Stahl-Hennig Christiane,Abicht Jan-Michael
Abstract
AbstractXenotransplantation using pig organs has achieved survival times up to 195 days in pig orthotopic heart transplantation into baboons. Here we demonstrate that in addition to an improved immunosuppressive regimen, non-ischaemic preservation with continuous perfusion and control of post-transplantation growth of the transplant, prevention of transmission of the porcine cytomegalovirus (PCMV) plays an important role in achieving long survival times. For the first time we demonstrate that PCMV transmission in orthotopic pig heart xenotransplantation was associated with a reduced survival time of the transplant and increased levels of IL-6 and TNFα were found in the transplanted baboon. Furthermore, high levels of tPA-PAI-1 complexes were found, suggesting a complete loss of the pro-fibrinolytic properties of the endothelial cells. These data show that PCMV has an important impact on transplant survival and call for elimination of PCMV from donor pigs.
Publisher
Springer Science and Business Media LLC
Subject
Multidisciplinary
Reference86 articles.
1. Längin, M., Mayr, T., Reichart, B., Michel, S., Buchholz, S., Guethoff, S., Dashkevich, A., Baehr, A., Egerer, S., Bauer, A., Mihalj, M., Panelli, A., Issl, L., Ying, J., Fresch, A. K., Buttgereit, I., Mokelke, M., Radan, J., Werner, F., Lutzmann, I., Steen, S., Sjöberg, T., Paskevicius, A., Qiuming, L., Sfriso, R., Rieben, R., Dahlhoff, M., Kessler, B., Kemter, E., Klett, K., Hinkel, R., Kupatt, C., Falkenau, A., Reu, S., Ellgass, R., Herzog, R., Binder, U., Wich, G., Skerra, A., Ayares, D., Kind, A., Schönmann, U., Kaup, F. J., Hagl, C., Wolf, E., Klymiuk, N., Brenner, P. & Abicht, J. M. Consistent success in life-supporting porcine cardiac xenotransplantation. Nature 564(7736), 430–433 (2018). 2. Denner, J. & Tönjes, R. R. Infection barriers to successful xenotransplantation focusing on porcine endogenous retroviruses. Clin Microbiol Rev. 25(2), 318–343 (2012). 3. Wynyard, S., Nathu, D., Garkavenko, O., Denner, J. & Elliott, R. Microbiological safety of the first clinical pig islet xenotransplantation trial in New Zealand. Xenotransplantation 21(4), 309–323 (2014). 4. Morozov, V. A. et al. No PERV transmission during a clinical trial of pig islet cell transplantation. Virus Res. 227, 34–40 (2017). 5. Harrison, I., Takeuchi, Y., Bartosch, B. & Stoye, J. P. Determinants of high titer in recombinant porcine endogenous retroviruses. J. Virol. 78(24), 13871–13879 (2004).
Cited by
61 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
|
|