Long-term Functioning of Allogeneic Islets in Subcutaneous Tissue Pretreated With a Novel Cyclic Peptide Without Immunosuppressive Medication
Long-term Functioning of Allogeneic Islets in Subcutaneous Tissue Pretreated With a Novel Cyclic Peptide Without Immunosuppressive Medication
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DOI：
10.1097/tp.0000000000001923
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发表时间：
2017-08
期刊：
影响因子：
6.2
通讯作者：
Rei Kuwabara;M. Hamaguchi;Takuya Fukuda;Hiroki Sakai;M. Inui;S. Sakaguchi;H. Iwata
中科院分区：
文献类型：
--
作者：
Rei Kuwabara;M. Hamaguchi;Takuya Fukuda;Hiroki Sakai;M. Inui;S. Sakaguchi;H. Iwata
背景目前需要一种不使用免疫抑制药物的微创胰岛移植方法来治疗1型糖尿病。方法将含有环状寡肽SEK-1005的琼脂糖棒（agarose-SEK rod）植入糖尿病August Copenhagen Irish大鼠背部皮下2个部位。然后将这些杆取出，并将从Fischer 344大鼠分离的1500个胰岛移植到每个口袋中。结果琼脂糖-SEK棒植入后10天，出现血管化囊袋。非空腹血糖水平证实了10例受者中有8例在没有免疫抑制治疗的情况下同种异体胰岛移植物的长期存活。流式细胞术和基因表达分析进行了研究移植物接受的机制。琼脂糖-SEK棒植入导致肉芽肿组织的形成，该肉芽肿组织含有抑制针对同种异体胰岛移植物的免疫反应的调节性T细胞。结论这些结果表明，使用琼脂糖-SEK棒预血管化皮下部位可能是一种有用的方法，实现成功的同种异体胰岛移植无免疫抑制。
Background There exists a need for a minimally invasive method of islet transplantation without immunosuppressive drugs for the treatment of type 1 diabetes. Methods In diabetic August Copenhagen Irish rats, an agarose rod containing the cyclic oligopeptide SEK-1005 (agarose-SEK rod) was implanted at 2 dorsal subcutaneous sites. Then these rods were removed, and 1500 islets of Langerhans isolated from Fischer 344 rats were transplanted into each of the pockets. Results Ten days after implantation of agarose-SEK rods, vascularized pockets were present. Nonfasting blood glucose levels confirmed long-term survival of the allogeneic islet grafts, without immunosuppressive therapy, in 8 of 10 recipients. Flow cytometry and gene expression analyses were performed to investigate the mechanisms underlying graft acceptance. Agarose-SEK rod implantation led to the formation of granulomatous tissue containing regulatory T cells that suppressed immune reactions against the allogeneic islet grafts. Conclusions These results indicate that the use of an agarose-SEK rod to prevascularize a subcutaneous site may be a useful method for achieving successful allogeneic islet transplantation without immunosuppression.