Aghajani-Lazarjani Hamideh, Vasheghani-Farahani Ebrahim, Hashemi-Najafabadi Sameereh, Shojaosadati Seyed Abbas, Zahediasl Saleh, Tiraihi Taki, Atyabi Fatemeh
Biotechnology Group, Department of Chemical Engineering, Faculty of Engineering, Tarbiat Modares University, P.O. Box 14115-143, Tehran, 1411713116, Iran.
Endocrine Physiology Laboratory, Endocrine Research Centre, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, 3197619751, Iran.
Prog Biomater. 2013 Mar 9;2(1):7. doi: 10.1186/2194-0517-2-7.
Langerhans islet transplantation is a much less invasive approach compared with the pancreas transplantation to 'cure' diabetes. However, destruction of transplanted islets by the immune system is an impediment for a successful treatment. Chemical grafting of monomethoxy poly(ethylene glycol) onto pancreatic islet capsule is a novel approach in islet immunoisolation. The aim of this study was to determine an optimized condition for grafting of monomethoxy poly(ethylene glycol) succinimidyl propionate (mPEG-SPA) on islets capsule. Independent variables such as reaction time, the percentage of longer mPEG in the mixture, and polymer concentration were optimized using a three-factor, three-level Box-Behnken statistical design. The dependent variable was IL-2 (interleukin-2) secretion of lymphocytes co-cultured with PEGylated or uncoated control islets for 7 days co-culturing. A mathematical relationship is obtained which explained the main and quadratic effects and the interaction of factors which affected IL-2 secretion. Response surface methodology predicted the optimized values of reaction time, the percentage of longer mPEG in the mixture, and polymer concentration of 60 min to be 63.7% mPEG and 22 mg/mL, respectively, for the minimization of the secreted IL-2 as response. Islets which were PEGylated at this condition were transplanted to diabetic rats. The modified islets could survive for 24 days without the aid of any immunosuppressive drugs and it is the longest survival date reported so far. However, free islets (unmodified islets as control) are completely destroyed within 7 days. These results strongly suggest that this new protocol provides an effective clinical means of decreasing transplanted islet immunogenicity.
与胰腺移植相比，胰岛移植是一种侵入性小得多的“治愈”糖尿病的方法。然而，免疫系统对移植胰岛的破坏是成功治疗的一个障碍。将单甲氧基聚（乙二醇）化学接枝到胰岛包膜上是胰岛免疫隔离的一种新方法。本研究的目的是确定在胰岛包膜上接枝单甲氧基聚（乙二醇）琥珀酰亚胺丙酸酯（mPEG-SPA）的优化条件。使用三因素、三水平的Box-Behnken统计设计对反应时间、混合物中较长mPEG的百分比和聚合物浓度等自变量进行优化。因变量是与聚乙二醇化或未包被的对照胰岛共培养7天的淋巴细胞的白细胞介素-2（IL-2）分泌。得到了一个数学关系模型，该模型解释了影响IL-2分泌的主要和二次效应以及各因素之间的相互作用。响应面法预测，以分泌的IL-2最小化为响应指标，反应时间、混合物中较长mPEG的百分比和聚合物浓度的优化值分别为60分钟、63.7%的mPEG和22mg/mL。在此条件下聚乙二醇化的胰岛被移植到糖尿病大鼠体内。经修饰的胰岛在不使用任何免疫抑制药物的情况下可以存活24天，这是迄今为止报道的最长存活时间。然而，游离胰岛（未修饰的胰岛作为对照）在7天内被完全破坏。这些结果强烈表明，这一新方案提供了一种降低移植胰岛免疫原性的有效临床手段。
