Kin Tatsuya, Rajotte Ray V, Dufour Jannette M, Korbutt Gregory S
Surgical-Medical Research Institute, University of Alberta, Edmonton, Canada.
Cell Transplant. 2002;11(6):547-52.
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.
支持细胞（SC）在维持睾丸的免疫豁免环境中起着关键作用。我们推测，预先植入支持细胞将使人们能够构建一个血管化的免疫豁免异位位点，为小鼠胰岛同种异体移植提供保护。从9日龄的Balb/c小鼠制备的支持细胞被移植到成年Balb/c小鼠的肾包膜下。在支持细胞植入后（约30天），使小鼠患糖尿病，随后将Balb/c或CBA/J胰岛直接植入已建立的支持细胞移植物附近。预先植入的支持细胞（5.7±0.2×10⁶）对同基因胰岛移植物功能没有不良影响。当将异基因胰岛移植到通过预先植入6.4±0.3×10⁶个支持细胞而创建的免疫豁免异位位点时，与仅接受异基因胰岛的对照小鼠相比，平均移植物存活时间略有延长（32.4±6.0天）（16.3±1.5天；p = 0.329）。相比之下，当预先植入4.8±0.4×10⁶个支持细胞时，胰岛同种异体移植存活时间显著延长（66.1±9.8天；p = 0.001）。在预先植入4.8±0.4×10⁶个支持细胞的八只小鼠中，有四只在整个随访期（83.8±8.6天）内保持血糖正常，仅在切除带有复合移植物的肾脏时才恢复到糖尿病状态。将胰岛移植到通过预先植入支持细胞而创建的免疫豁免异位位点不会影响胰岛功能，而且提供了一种构建免疫豁免异位位点的方法，该位点允许在不进行全身免疫抑制的情况下延长胰岛同种异体移植的存活时间。
