Impact of porcine cytomegalovirus on long-term orthotopic cardiac xenotransplant survival.
Animals
Animals, Genetically Modified
Cytomegalovirus
/ classification
Cytomegalovirus Infections
/ physiopathology
Endothelial Cells
Graft Survival
Heart Transplantation
/ adverse effects
Heterografts
Immune System
Immunosuppression Therapy
Immunosuppressive Agents
/ therapeutic use
Interleukin-6
/ metabolism
Papio
Swine
Transplantation, Heterologous
Tumor Necrosis Factor-alpha
/ metabolism
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
16 10 2020
16 10 2020
Historique:
received:
11
05
2020
accepted:
09
09
2020
entrez:
17
10
2020
pubmed:
18
10
2020
medline:
11
3
2021
Statut:
epublish
Résumé
Xenotransplantation 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.
Identifiants
pubmed: 33067513
doi: 10.1038/s41598-020-73150-9
pii: 10.1038/s41598-020-73150-9
pmc: PMC7568528
doi:
Substances chimiques
Immunosuppressive Agents
0
Interleukin-6
0
Tumor Necrosis Factor-alpha
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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