Development of an immunoprivileged site to prolong islet allograft survival.
Sertoli cells (SC) play a critical role in the maintenance of the immunoprivileged environment of the testis. We hypothesized that preengrafting SC would allow one to develop a vascularized immunoprivileged ectopic site that provides protection for mouse islet allografts. SC, prepared from 9-day Balb/c mice, were transplanted under the kidney capsule in adult Balb/c mice. After SC engraftment (approximately 30 days), mice were rendered diabetic and subsequently implanted with Balb/c or CBA/J islets directly adjacent to the established SC grafts. Preengrafted SC (5.7 +/- 0.2 x 106) had no adverse effect on syngeneic islet graft function. When allogeneic islets were transplanted into the immunoprivileged ectopic site created by preengrafting 6.4 +/- 0.3 x 10(6) SC, mean graft survival was slightly prolonged (32.4 +/- 6.0 days) compared with control mice that received allogeneic islets alone (16.3 +/- 1.5 days; p = 0.329). In contrast, when 4.8 +/- 0.4 x 10(6) SC were preengrafted, islet allograft survival was significantly prolonged (66.1 +/- 9.8 days; p = 0.001). Four of eight mice, preimplanted with 4.8 +/- 0.4 x 10(6) SC, remained normoglycemic throughout the follow-up period (83.8 +/- 8.6 days) and returned to a diabetic state only when the kidneys bearing the composite grafts were removed. Transplantation of islets into an immunoprivileged ectopic site created by preengrafting SC did not affect islet function and, moreover, provided a means of developing an immunopriveliged ectopic site that permits prolonged islet allograft survival without systemic immunosuppression.
Kin
Tatsuya
T
Surgical-Medical Research Institute, University of Alberta, Edmonton, Canada.
Rajotte
Ray V
RV
Dufour
Jannette M
JM
Korbutt
Gregory S
GS
D000818:Animals; D002470:Cell Survival; D006085:Graft Survival / Q000276:immunology*; D016381:Islets of Langerhans Transplantation / Q000276:immunology* / Q000379:methods; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D009928:Organ Specificity; D012708:Sertoli Cells / Q000166:cytology / Q000637:transplantation; D013370:Subrenal Capsule Assay / Q000379:methods; D013997:Time Factors; D014184:Transplantation, Homologous; D014185:Transplantation, Isogeneic