Immobilization of urokinase on the islet surface by amphiphilic poly(vinyl alcohol) that carries alkyl side chains
Immobilization of urokinase on the islet surface by amphiphilic poly(vinyl alcohol) that carries alkyl side chains
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DOI：
10.1016/j.biomaterials.2008.03.024
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发表时间：
2008-07-01
期刊：
影响因子：
14
通讯作者：
Iwata, Hiroo
中科院分区：
文献类型：
--
作者：
Totani, Takahiko;Teramura, Yuji;Iwata, Hiroo
胰岛移植是治疗胰岛素依赖型糖尿病(I型糖尿病)的一种有前景的方法。然而，通常只有30%的移植受者实现胰岛素独立，即使有足够数量的来自多个捐赠者的胰岛。凝血引发的先天免疫反应在早期胰岛丢失中起关键作用。在此，我们提出了一种抑制胰岛表面凝血的方法。纤溶酶原激活剂尿激活剂通过带有烷基链和硫醇基团的聚乙烯醇(PVA)衍生物固定在胰岛表面。当PVA衍生物被添加到胰岛悬浮液中时，烷基侧链自发地锚定到胰岛细胞的脂质双层膜上。胰岛表面覆盖PVA衍生物。用马来酰亚胺修饰的尿激酶可以通过硫醇/马来酰亚胺与PVA衍生层键合的方式固定在胰岛表面。尿激酶固定化的胰岛表现出纤溶特性，表明胰岛表面的凝血是可以控制的。胰岛尿激酶固定化不影响胰岛素的释放，是减少门静脉胰岛移植术后早期移植物丢失的一种有前景的方法。(C)2008爱思唯尔有限公司。保留所有权利。
Transplantation of islets of Langerhans (islets) is a promising method to treat insulin-dependent diabetes mellitus (type I diabetes). However, insulin independence is typically realized for only similar to 30% of transplant recipients, even with sufficient numbers of islets from multiple donors. Innate immunological reactions triggered by blood coagulation play a key role in the loss of islets at the early stage. Here we propose a method to inhibit blood coagulation on the islet surface. A plasminogen activator, urokinase, was immobilized on the islet surface via a poly(vinyl alcohol) (PVA) derivative that carries alkyl chains and thiol groups. When the PVA derivative was added to an islet suspension, the alkyl side chains spontaneously anchored into the lipid bilayer membranes of islet cells. The surfaces of islets were covered with the PVA derivative. Urokinase modified with maleimide groups could be immobilized onto the islet surface by thiol/maleimide bonding with the layer of PVA derivatives. Urokinase-immobilized islets exhibited fibrinolytic properties, indicating that blood coagulation can be controlled on the islet surface. Urokinase immobilization on islets, which does not impair insulin release, represents a promising method to reduce early graft loss after intraportal islet transplantation. (C) 2008 Elsevier Ltd. All rights reserved.