No transmission of porcine endogenous retrovirus after transplantation of adult porcine islets into diabetic nude mice and immunosuppressed rats.
BACKGROUND
The aim of this study was to investigate whether transmission of porcine endogenous retrovirus (PERV) occurs in a model of diabetes reversal by the xenotransplantation of adult porcine islets (APIs) into immunoincompetent diabetic rodents.


METHODS
Black-6 nu/nu mice and Lewis rats were immunosuppressed with cyclosporin A (CsA) and FTY 720, and rendered diabetic with streptozotocin. Purified APIs were transplanted into the renal subcapsular space; 5,000 islet equivalents (IEQs) were used in the nude mice (n = 4) and 40,000 IEQs in the rats (n = 4). The nude mice were sacrificed at 75 days after transplantation. In order to confirm chronic xenograft function, the graft-bearing kidney was removed prior to sacrifice. The rats were followed until xenograft rejection, at which time they were sacrificed. Immediately after sacrifice, tissue samples (liver, spleen, and small intestine) were taken for analysis. Quantitative polymerase chain reaction (PCR) was used to assess evidence of PERV transmission, and porcine cell chimerism.


RESULTS
All animals became normoglycemic within 48 h of transplantation. The nude mice remained normoglycemic during the 75-day study period, with removal of the graft-bearing kidney resulting in prompt hyperglycemia. The rats remained normoglycemic until xenograft rejection, which occurred at 66 +/- 28 days. Despite the evidence of porcine cell microchimerism in recipients, real-time PCR detected no evidence of PERV transmission in any of the tissue specimens tested.


CONCLUSIONS
There was no evidence of PERV transmission following transplantation of pig islets into diabetic nude mice and immunosuppressed rats.
Goto
Masafumi
M
Department of Transplantation Surgery, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden. gotokichi@aol.com
Maeda
Akira
A
Elfman
Lotta
L
Suling
Kristen M
KM
Wood
James C
JC
Patience
Clive
C
Groth
Carl G
CG
Wennberg
Lars
L
D000375:Aging / Q000502:physiology; D000818:Animals; D002469:Cell Separation; D046528:Chimerism; D012321:DNA-Directed RNA Polymerases / Q000235:genetics; D003920:Diabetes Mellitus / Q000601:surgery*; D020077:Endogenous Retroviruses / Q000235:genetics* / Q000302:isolation & purification; D016867:Immunocompromised Host / Q000276:immunology*; D016381:Islets of Langerhans Transplantation; D008297:Male; D051379:Mice; D008819:Mice, Nude; D051381:Rats; D012192:Retroviridae Infections / Q000662:veterinary / Q000821:virology; D013552:Swine / Q000235:genetics* / Q000821:virology*; D014180:Transplantation; D014183:Transplantation, Heterologous
D012321:DNA-Directed RNA Polymerases