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Development of an Immunoprivileged Site to Prolong Islet Allograft Survival

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Abstract:

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 (∼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 × 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 × 106 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 × 106 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 × 106 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.

Keywords: D; Islet transplantation; Key words: Sertoli cells

Document Type: Research Article

DOI: http://dx.doi.org/10.3727/000000002783985585

Affiliations: Surgical-Medical Research Institute, 1074 Dentistry/Pharmacy Building, University of Alberta, Edmonton, Alberta, Canada T6G 2N8

Publication date: January 1, 2002

More about this publication?
  • Cell Transplantation publishes original, peer-reviewed research and review articles on the subject of cell transplantation and its application to human diseases. To ensure high-quality contributions from all areas of transplantation, separate section editors and editorial boards have been established. Articles deal with a wide range of topics including physiological, medical, preclinical, tissue engineering, and device-oriented aspects of transplantation of nervous system, endocrine, growth factor-secreting, bone marrow, epithelial, endothelial, and genetically engineered cells, among others. Basic clinical studies and immunological research papers are also featured. To provide complete coverage of this revolutionary field, Cell Transplantation will report on relevant technological advances, and ethical and regulatory considerations of cell transplants. Cell Transplantation is now an Open Access journal starting with volume 18 in 2009, and therefore there will be an inexpensive publication charge, which is dependent on the number of pages, in addition to the charge for color figures. This will allow work to be disseminated to a wider audience and also entitle the corresponding author to a free PDF, as well as prepublication of an unedited version of the manuscript.
cog/ct/2002/00000011/00000006/ct323
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