Analysis of pig-to-human porcine endogenous retrovirus transmission in a triple-species kidney xenotransplantation model.
Clinical pig-to-human xenotransplantation might be associated with the risk of transmission of xenozoonoses, especially porcine endogenous retroviruses (PERVs). We have established a pig-to-humanised-cynomolgus monkey xenotransplantation model allowing the analysis of potential PERV-transmission from normal or transgenic porcine organs to human vascular tissue. Pig-to-human kidney xenotransplantation was performed in cynomolgus monkeys. An interposition graft constructed from a human saphena vein replaced the porcine kidney vein. After graft rejection and/or death of the recipient (survival 2, 4, 6, 13, 16, 19 days), the human interposition grafts were removed. Human endothelial cells (huECs) were isolated from the interposition grafts and cultivated in vitro. Explanted human vascular tissue, isolated huECs, plasma and serum samples of the graft recipients were characterised by flow cytometry and immunohistochemistry and screened for indications of PERV transmission by quantitative polymerase chain reaction (PCR), reverse transcriptase-polymerase chain reaction (RT-PCR) and RT assay. PERV-specific immune response of recipients was analysed by Western blot. No evidence of PERV infection or PERV-specific immune response was detected.
Winkler
Monica E
ME
Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Hannover, Germany. winkler.monica@mh-hannover.de
Winkler
Michael
M
Burian
Rosemarie
R
Hecker
Jens
J
Loss
Martin
M
Przemeck
Michael
M
Lorenz
Ralf
R
Patience
Clive
C
Karlas
Alexander
A
Sommer
Sebastian
S
Denner
Joachim
J
Martin
Ulrich
U
D000818:Animals; D002470:Cell Survival; D002478:Cells, Cultured; D020077:Endogenous Retroviruses; D042783:Endothelial Cells / Q000166:cytology / Q000821:virology; D005434:Flow Cytometry; D006084:Graft Rejection / Q000821:virology; D006085:Graft Survival; D006801:Humans; D016030:Kidney Transplantation / Q000009:adverse effects*; D008252:Macaca fascicularis; D011183:Postoperative Complications / Q000821:virology; D013552:Swine; D014183:Transplantation, Heterologous / Q000009:adverse effects*; D015047:Zoonoses / Q000635:transmission* / Q000821:virology*