The Efficacy of a Prevascularized, Retrievable Poly(D,L,-lactide-co-ε-caprolactone) Subcutaneous Scaffold as Transplantation Site for Pancreatic Islets
The Efficacy of a Prevascularized, Retrievable Poly(D,L,-lactide-co-ε-caprolactone) Subcutaneous Scaffold as Transplantation Site for Pancreatic Islets
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DOI：
10.1097/tp.0000000000001663
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发表时间：
2017-04-01
期刊：
影响因子：
6.2
通讯作者：
de Vos, Paul
中科院分区：
文献类型：
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作者：
Smink, Alexandra M.;Li, Shiri;de Vos, Paul
背景作为人胰岛移植部位的肝脏对胰岛来说是一个苛刻的微环境，并且它缺乏回收移植物的能力。一个可回收的，肝外移植部位，模仿胰腺环境是理想的。理想情况下，该移植部位应位于真皮下，以便于药物进入，但这从未导致正常免疫反应。在这里，我们描述了一种新的预血管化，皮下植入，可回收的聚（D，L-丙交酯-共-ε-己内酯）支架的设计和疗效。法将三种剂量的大鼠胰岛，即400、800和1200，植入免疫受损小鼠中以测试功效（n = 5）。以肾包膜下胰岛移植为对照组（n = 5）。通过非空腹血糖测量和葡萄糖耐量试验确定疗效。结果将800个（n = 5）和1200个胰岛（n = 5）移植到支架中分别在移植后6.8至18.5天内在80%和100%的小鼠中逆转了糖尿病。400个胰岛（n = 5）的边缘剂量诱导20%的正常胰岛。葡萄糖耐量试验显示，与糖尿病对照组相比，支架组的葡萄糖清除率有显著改善。然而，肾包膜稍微更有效，因为所有800个（n = 5）和1200个胰岛（n = 5）接受者和400个胰岛（n = 5）接受者中的40%在8天内变得血糖正常。移除支架或肾脏移植物导致高血糖症立即恢复。在未修饰皮肤组中，1200个胰岛没有达到正常的生长。结论.我们的研究结果表明，预血管化的聚（D，L-丙交酯-共-ε-己内酯）支架在皮下部位保持胰岛的活力和功能。
Background. The liver as transplantation site for human pancreatic islets is a harsh microenvironment for islets and it lacks the ability to retrieve the graft. A retrievable, extrahepatic transplantation site that mimics the pancreatic environment is desired. Ideally, this transplantation site should be located subdermal for easy surgical-access but this never resulted in normoglycemia. Here, we describe the design and efficacy of a novel prevascularized, subcutaneously implanted, retrievable poly (D,L-lactide-co-epsilon-caprolactone) scaffold. Method. Three dosages of rat islets, that is, 400, 800, and 1200, were implanted in immune compromised mice to test the efficacy (n = 5). Islet transplantation under the kidney capsule served as control (n = 5). The efficacy was determined by nonfasting blood glucose measurements and glucose tolerance tests. Results. Transplantation of 800 (n = 5) and 1200 islets (n = 5) into the scaffold reversed diabetes in respectively 80 and 100% of the mice within 6.8 to 18.5 days posttransplant. The marginal dose of 400 islets (n = 5) induced normoglycemia in 20%. The glucose tolerance test showed major improvement of the glucose clearance in the scaffold groups compared to diabetic controls. However, the kidney capsule was slightly more efficacious because all 800 (n = 5) and 1200 islets (n = 5) recipients and 40% of the 400 islets (n = 5) recipients became normoglycemic within 8 days. Removal of the scaffolds or kidney grafts resulted in immediate return to hyperglycemia. Normoglycemia was not achieved with 1200 islets in the unmodified skin group. Conclusions. Our findings demonstrate that the prevascularized poly (D,L-lactide-co-epsilon-caprolactone) scaffold maintains viability and function of islets in the subcutaneous site.