Gustafson Elisabet, Asif Sana, Kozarcanin Huda, Elgue Graciela, Meurling Staffan, Ekdahl Kristina N, Nilsson Bo
Cell Transplant. 2017 Jan 24;26(1):71-81. doi: 10.3727/096368916X692609. Epub 2016 Jul 22.
Rapid destruction of hepatocytes after hepatocyte transplantation has hampered the application of this procedure clinically. The instant blood-mediated inflammatory reaction (IBMIR) is a plausible underlying cause for this cell loss. The present study was designed to evaluate the capacity of low molecular weight dextran sulfate (LMW-DS) to control these initial reactions from the innate immune system. Fresh and cryopreserved hepatocytes were tested in an in vitro whole-blood model using ABO-compatible blood. The ability to elicit IBMIR and the capacity of LMW-DS (100 μg/ml) to attenuate the degree of activation of the cascade systems were monitored. The effect was also compared to conventional anticoagulant therapy using unfractionated heparin (1 IU/ml). Both fresh and freeze-thawed hepatocytes elicited IBMIR to the same extent. LMW-DS reduced the platelet loss and maintained the cell counts at the same degree as unfractionated heparin, but controlled the coagulation and complement systems significantly more efficiently than heparin. LMW-DS also attenuated the IBMIR elicited by freeze-thawed cells. Therefore, LMW-DS inhibits the cascade systems and maintains the cell counts in blood triggered by both fresh and cryopreserved hepatocytes in direct contact with ABO-matched blood. LMW-DS at a previously used and clinically applicable concentration (100 μg/ml) inhibits IBMIR in vitro and is therefore a potential IBMIR inhibitor in hepatocyte transplantation.
肝细胞移植后肝细胞的快速破坏阻碍了该方法在临床上的应用。即时血液介导的炎症反应（IBMIR）可能是导致这种细胞损失的潜在原因。本研究旨在评估低分子量硫酸葡聚糖（LMW-DS）控制先天免疫系统这些初始反应的能力。使用ABO血型相容的血液，在体外全血模型中对新鲜和冷冻保存的肝细胞进行测试。监测引发IBMIR的能力以及LMW-DS（100μg/ml）减弱级联系统激活程度的能力。还将该效果与使用普通肝素（1IU/ml）的传统抗凝治疗进行比较。新鲜和冻融的肝细胞引发IBMIR的程度相同。LMW-DS减少了血小板损失，并与普通肝素一样维持细胞计数，但在控制凝血和补体系统方面比肝素更有效。LMW-DS还减弱了冻融细胞引发的IBMIR。因此，LMW-DS抑制级联系统，并维持与ABO血型匹配的血液直接接触的新鲜和冷冻保存的肝细胞在血液中的细胞计数。先前使用的且临床适用浓度（100μg/ml）的LMW-DS在体外抑制IBMIR，因此是肝细胞移植中潜在的IBMIR抑制剂。
