Low molecular weight dextran sulfate: A strong candidate drug to block IBMIR in clinical islet transplantation
Low molecular weight dextran sulfate: A strong candidate drug to block IBMIR in clinical islet transplantation
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DOI：
10.1111/j.1600-6143.2005.01186.x
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发表时间：
2006-02-01
影响因子：
8.8
通讯作者：
Nilsson, B
中科院分区：
文献类型：
--
作者：
Johansson, H;Goto, M;Nilsson, B
在临床胰岛移植中，当人胰岛与血液接触时会引发即时血液介导的炎症反应（IBMIR），这可能解释了与该手术相关的初始组织损失。低分子量硫酸葡聚糖（LMW - DS；分子量5000）目前可用于临床，它能抑制补体和凝血激活。在管环模型中，浓度在0.01至1 g/L范围内的LMW - DS对IBMIR呈剂量依赖性抑制，可抑制凝血和补体激活，并减少血小板和其他血细胞的消耗。在血液或血浆中，活化部分凝血活酶时间（APTT）被证明是在体外和非人灵长类动物模型体内监测LMW - DS浓度的极佳方法。使用葡萄糖激发试验评估毒性，并在非人灵长类动物模型中测试药代动力学。在此，我们提出了在临床胰岛移植中使用LMW - DS的初步方案。
The instant blood-mediated inflammatory reaction (IBMIR) is triggered in clinical islet transplantation when human pancreatic islets come in contact with blood and may explain the initial tissue loss associated with this procedure. Low molecular weight dextran sulfate (LMW-DS; MM 5000), today available for clinical use, inhibits both complement and coagulation activation. In a tubing loop model, LMW-DS at concentrations ranging from 0.01 to 1 g/L showed a dose-dependent inhibition of IBMIR with an inhibition of coagulation and complement activation and less consumption of platelets and other blood cells. In blood or plasma APTT was demonstrated to be an excellent method for monitoring the LMW-DS concentration both in vitro and in vivo in a nonhuman primate model. The toxicity was assessed using a glucose challenge test and the pharmacokinetics was tested in the nonhuman primate model. Here, we present a tentative protocol for using LMW-DS in clinical islet transplantation.