Smink Alexandra M, Li Shiri, Hertsig Don T, de Haan Bart J, Schwab Leendert, van Apeldoorn Aart A, de Koning Eelco, Faas Marijke M, Lakey Jonathan R T, de Vos Paul
1 Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. 2 Department of Surgery, University of California Irvine, Orange, CA. 3 Polyganics, Groningen, The Netherlands. 4 Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. 5 Department of Developmental BioEngineering, Faculty of Science and Technology, University of Twente, Enschede, The Netherlands. 6 Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands. 7 Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. 8 Department of Obstetrics and Gynaecology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. 9 Department of Biomedical Engineering, University of California Irvine, Irvine, CA. 10 Department of Surgery, University of California Irvine, Orange, CA. 11 Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Transplantation. 2017 Apr;101(4):e112-e119. doi: 10.1097/TP.0000000000001663.
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-ε-caprolactone) scaffold.
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.
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.
Our findings demonstrate that the prevascularized poly (D,L-lactide-co-ε-caprolactone) scaffold maintains viability and function of islets in the subcutaneous site.
肝脏作为人类胰岛移植的部位，对胰岛来说是一个恶劣的微环境，且它缺乏恢复移植器官的能力。因此需要一个可恢复的、模仿胰腺环境的肝外移植部位。理想情况下，这个移植部位应位于皮下以便于手术操作，但这从未导致正常血糖水平。在此，我们描述一种新型的预血管化、皮下植入、可恢复的聚（D，L-丙交酯-共-ε-己内酯）支架的设计及效果。
将三种剂量的大鼠胰岛，即400、800和1200个，植入免疫受损小鼠体内以测试效果（n = 5）。将胰岛移植到肾被膜下作为对照（n = 5）。通过非空腹血糖测量和葡萄糖耐量试验来确定效果。
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天内使80%和100%的小鼠糖尿病得到逆转。400个胰岛的边缘剂量（n = 5）使20%的小鼠出现正常血糖。葡萄糖耐量试验表明，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，肾被膜组的效果稍好一些，因为所有接受800个（n = 5）和1200个胰岛（n = 5）的小鼠以及40%接受400个胰岛（n = 5）的小鼠在8天内血糖恢复正常。移除支架或肾移植物后，血糖立即恢复到高血糖水平。在未改良的皮肤组中，1200个胰岛未实现正常血糖水平。
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）支架在皮下部位能维持胰岛的活力和功能。
