Subcutaneous transplantation of macroencapsulated porcine pancreatic endocrine cells normalizes hyperglycemia in diabetic mice1
Subcutaneous transplantation of macroencapsulated porcine pancreatic endocrine cells normalizes hyperglycemia in diabetic mice1
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大封装猪胰腺内分泌细胞的皮下移植使糖尿病小鼠的高血糖正常化1
DOI：
10.1097/01.tp.0000073613.25658.4d
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发表时间：
2003
期刊：
影响因子：
6.2
通讯作者：
Kazutomo Inoue
中科院分区：
文献类型：
--
作者：
Wenjing Wang;Yuanjun Gu;H. Hori;T. Sakurai;A. Hiura;S. Sumi;Y. Tabata;Kazutomo Inoue
背景资料。胰岛移植的最终目标是无限制地获得胰岛素分泌细胞，通过一种不需要使用免疫抑制药物的简单程序进行移植。异种猪胰岛的免疫分离移植在治疗糖尿病方面具有很大的潜在治疗价值。方法：研究方法。从6月龄猪分离出约4×106个猪胰腺内分泌细胞(PEC)，用琼脂糖-聚苯磺酸混合凝胶包埋于链脲佐菌素诱导的C57BL/6糖尿病小鼠的皮下。接受相同数量的免费猪PEC的动物作为对照。移植后进行非空腹血糖、体重、腹膜糖耐量试验和免疫组织学评价。结果。10只接受大囊化猪PEC皮下移植的动物均在移植后5天内血糖恢复正常，并维持正常血糖24~76天，并逐渐增加体重。游离猪PEC皮下移植不能逆转高血糖。移植后第45天，当移植的移植物被取回时，受者再次出现高血糖。与糖尿病小鼠相比，移植后第21天和第45天的葡萄糖清除量显著改善。免疫组织化学结果显示，大囊化猪PEC结构完整，胰岛素和胰升糖素双重免疫荧光染色阳性。结论。大囊化猪PEC皮下移植对糖尿病小鼠高血糖的影响。我们的结果证实了猪PEC皮下移植作为治疗糖尿病的良好发展的潜力。
Background. 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. Methods. Approximately 4×106 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. Results. 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. Conclusions. 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.
影响因子：
2.7
作者：
Swanson,CJ;Olack,BJ;Goodnight,D;Zhang,L;Mohanakumar,T
通讯作者：
Mohanakumar,T