Wang Wenjing, Gu Yuanjun, Hori Hiroshi, Sakurai Tomonori, Hiura Akihito, Sumi Shoichiro, Tabata Yasuhiko, Inoue Kazutomo
Department of Organ Reconstruction, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan.
Transplantation. 2003 Jul 27;76(2):290-6. doi: 10.1097/01.TP.0000073613.25658.4D.
The ultimate goal of islet transplantation is the unlimited availability of insulin-secreting cells to be transplanted in a simple procedure that requires no use of immunosuppressive drugs. Immunoisolation of xenogeneic pig islets for transplantation has great potential therapeutic benefits for treatment of diabetes.
Approximately 4 x 10(6) porcine pancreatic endocrine cells (PEC) isolated from 6-month-old pigs were macroencapsulated in agarose-poly(styrene sulfonic acid) mixed gel and implanted into a prevascularized subcutaneous site in streptozotocin-induced C57BL/6 diabetic mice. Animals receiving an equal number of free porcine PEC were used as controls. After transplantation, nonfasting blood glucose, body weight, intraperitoneal glucose tolerance test, and immunohistologic evaluations were processed.
All 10 animals receiving the subcutaneous xenografts of the macroencapsulated porcine PEC normalized hyperglycemia within 5 days after transplantation, maintained the duration of normoglycemia for 24 to 76 days, and gradually gained weight. The subcutaneous xenografts of free porcine PEC could not reverse hyperglycemia. The recipient became hyperglycemic again when the implanted graft was retrieved at day 45 after transplantation. The glucose clearances were significantly ameliorated at day 21 and day 45 after transplantation when compared with those in diabetic mice. The immunohistochemical results revealed an inherent intact structure of the macroencapsulated porcine PEC and positive double-immunofluorescence staining for insulin and glucagon.
Subcutaneous transplantation of macroencapsulated porcine PEC normalized hyperglycemia in diabetic mice. Our results identified a potential for a favorable development of subcutaneous transplantation of porcine PEC as a cure for diabetes.
胰岛移植的最终目标是通过简单的程序获得无限量可用于移植的胰岛素分泌细胞，且无需使用免疫抑制药物。对用于移植的异种猪胰岛进行免疫隔离，对于糖尿病治疗具有巨大的潜在治疗益处。
从6月龄猪分离出约4×10⁶个猪胰腺内分泌细胞（PEC），将其在琼脂糖 - 聚苯乙烯磺酸混合凝胶中进行大胶囊化，然后植入链脲佐菌素诱导的C57BL / 6糖尿病小鼠的预先血管化皮下部位。接受等量游离猪PEC的动物用作对照。移植后，对非空腹血糖、体重、腹腔葡萄糖耐量试验和免疫组织学评估进行处理。
所有10只接受大胶囊化猪PEC皮下异种移植的动物在移植后5天内高血糖恢复正常，正常血糖持续时间为24至76天，并逐渐增重。游离猪PEC的皮下异种移植不能逆转高血糖。当在移植后第45天取出植入的移植物时，受体再次出现高血糖。与糖尿病小鼠相比，移植后第21天和第45天葡萄糖清除率显著改善。免疫组织化学结果显示大胶囊化猪PEC具有固有的完整结构，胰岛素和胰高血糖素双重免疫荧光染色呈阳性。
大胶囊化猪PEC皮下移植使糖尿病小鼠的高血糖恢复正常。我们的结果表明猪PEC皮下移植作为糖尿病治疗方法具有良好发展的潜力。
