Successful engraftment of autologous and allogeneic islets into the porcine thymus.
Work in rodents has shown that injection of pancreatic islets of Langerhans into the thymus can induce donor-specific unresponsiveness to islets subsequently transplanted to extrathymic sites. The overall objective of our investigation is to test this in a large animal (pig) model. In the current study we examined whether autologous and allogeneic adult or fetal islets survive in the porcine thymus. Collagenase-digested adult and fetal porcine islets were injected into the thymic lobes of 5- to 13-month-old, normal pigs. Pigs receiving allografts were given either a standard triple regimen of oral cyclosporine, azathioprine, and prednisone or intravenous anti-lymphocyte globulin (ALG) for immunosuppression. Two pigs of each group that received an allograft or autograft were given no immunosuppression. Biopsies of the grafts were taken at 4, 6, or 12 weeks for examination. Islet survival was assessed by histology with hematoxylin and eosin and insulin staining and by measurement of tissue insulin content using acid alcohol extraction and radioimmunoassay. The insulin content of control thymus was found to be 0.71 +/- 0.29 microU/mg (n = 5). The insulin content of the islet-grafted thymic tissues ranged from 1.57 to 10.65 microU/mg. Since the amounts of injected islets were not equal and not distributed evenly, and only a part of the graft site was used for determination of tissue insulin, thymic insulin contents higher than 1.4 microU/mg (twice that of the control value) were considered to demonstrate the presence of viable islets. With this criterion, we concluded that islets were found to be viable in seven of nine pigs and two pigs which were treated with ALG were shown to be marginally positive. On histological examination, islets were found in the thymus as well as under the thymic capsule, except for the above two pigs. These results demonstrate that the pig thymus supports fetal and adult islet transplants.
Watt
P C
PC
Department of Surgery, UCLA School of Medicine 90024.
Mullen
Y
Y
Nomura
Y
Y
Watanabe
Y
Y
Brunicardi
F C
FC
Anderson
C
C
Zinner
M J
MJ
Passaro
E P
EP
D000818:Animals; D001706:Biopsy; D005260:Female; D016332:Fetal Tissue Transplantation; D006085:Graft Survival; D007165:Immunosuppression Therapy; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000196:embryology*; D016381:Islets of Langerhans Transplantation; D008297:Male; D013552:Swine; D013556:Swine, Miniature; D013950:Thymus Gland / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous
D007328:Insulin