Tze W J, Tai J, Cheung S
Department of Pediatrics, University of British Columbia, Vancouver, Canada.
Transplantation. 1990 Mar;49(3):502-5. doi: 10.1097/00007890-199003000-00005.
Prolonged survival of human islet xenografts under the kidney capsule of diabetic rats was achieved. Human islet xenograft survival time for the nonimmunosuppressed and single-dose antithymocyte serum-treated rats were 3.7 +/- 0.33 days (mean +/- SE, n = 6) and 4.2 +/- 0.63 (n = 4), respectively. In the recipients given 5 doses of ATS after islet transplantation, the graft survival time was significantly prolonged to 18.2 +/- 1.9 days (n = 6). An intravenous glucose tolerance test was performed on 3 recipients with a functional graft 12 days after xenotransplantation. The mean K rate was 1.44 +/- 0.43 (n = 3) compared with that of 2.1 +/- 0.14 (n = 5) found in normal control rats. Human C-peptide was present in the rat recipients following islet transplantation. In addition all 3 recipients showed significant basal human C-peptide values posttransplant and achieved levels of above 2.4 ng/ml during IVGTT. Morphologic and immunohistochemical examination of the islet grafts show that in recipients without immunosuppression or with a single dose of ATS, there was marked degree of fibrosis with little endocrine tissue left in the graft area by day 5. In contrast, the xenograft from recipients treated with 5 doses of ATS still contained well-preserved islet tissue with many insulin and glucagon containing cells on the day of graft removal when blood glucose had returned to the hyperglycemic level. Infiltration of the graft area with lymphoid cells (OX1+, OX8+, and W3/25+) was prominent, but they were not detected within the islets. Staining with monoclonal antibody clone L243 did not detect any expression of human class II antigen on the human pancreatic endocrine cells undergoing rejection by the host. This study has shown that with adequate immunosuppression human islet xenograft can normalize the blood glucose with prolonged survival time in diabetic rat recipients. The discordant xenotransplantation model used in this study would be useful for future xenotransplantation studies.
人类胰岛异种移植在糖尿病大鼠肾被膜下实现了长期存活。未免疫抑制和单剂量抗胸腺细胞血清处理大鼠的人类胰岛异种移植存活时间分别为3.7±0.33天（平均值±标准误，n = 6）和4.2±0.63天（n = 4）。在胰岛移植后给予5剂抗胸腺细胞血清的受体中，移植物存活时间显著延长至18.2±1.9天（n = 6）。对3只移植后12天具有功能性移植物的受体进行了静脉葡萄糖耐量试验。平均K率为1.44±0.43（n = 3），而正常对照大鼠的平均K率为2.1±0.14（n = 5）。胰岛移植后大鼠受体中存在人C肽。此外，所有3只受体移植后基础人C肽值均显著升高，并且在静脉葡萄糖耐量试验期间达到2.4 ng/ml以上。胰岛移植物的形态学和免疫组织化学检查表明，在未免疫抑制或单剂量抗胸腺细胞血清处理的受体中，到第5天时，移植物区域出现明显程度的纤维化，内分泌组织所剩无几。相比之下，在血糖已恢复到高血糖水平的移植物切除当天，接受5剂抗胸腺细胞血清处理的受体的异种移植物仍含有保存良好的胰岛组织，其中有许多含胰岛素和胰高血糖素的细胞。移植物区域有明显的淋巴细胞（OX1 +、OX8 +和W3/25 +）浸润，但在胰岛内未检测到。用单克隆抗体克隆L243染色未检测到宿主排斥的人胰腺内分泌细胞上有人Ⅱ类抗原的任何表达。本研究表明，通过充分的免疫抑制，人类胰岛异种移植可使糖尿病大鼠受体的血糖正常化并延长存活时间。本研究中使用的不协调性异种移植模型将有助于未来的异种移植研究。
