Blocking porcine sialoadhesin improves extracorporeal porcine liver xenoperfusion with human blood.

Blocking porcine sialoadhesin improves extracorporeal porcine liver xenoperfusion with human blood.
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DOI:
10.1111/xen.12043
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发表时间:
2013-07
影响因子:
3.9
通讯作者:
Rees MA
Rees MA
中科院分区:
医学3区
文献类型:
--
作者:
Waldman JP;Vogel T;Burlak C;Coussios C;Dominguez J;Friend P;Rees MA

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暴发性肝衰竭患者目前在等待肝移植期间没有临时的支持手段。对于此类患者的潜在治疗方法是使用猪肝体外灌注作为“肝透析”的一种形式。在用人血体外灌注猪肝72小时期间,猪枯否细胞结合并吞噬人红细胞(hRBC),导致红细胞压积降低至原始值的2.5%。我们的实验室已经确定了猪sialoadhesin表达的枯否细胞作为凝集素负责结合N-乙酰神经氨酸的表面上的hRBC。我们评估了阻断猪唾液酸粘附素是否可以防止体外猪肝异种灌流过程中观察到的hRBC的识别和随后的破坏。在存在抗猪唾液酸粘附素抗体或同种型对照的情况下,使用用分离的hRBC灌注72小时的野生型猪肝进行离体研究。将抗猪唾液酸粘附素抗体添加到体外猪肝异种灌流模型中减少了72小时内hRBC的损失。在整个灌注过程中证明了持续的肝功能。本研究阐明了唾液酸粘附素在体外猪肝异种灌流模型中介导hRBC破坏的作用。
Patients in fulminant hepatic failure currently do not have a temporary means of support while awaiting liver transplantation. A potential therapeutic approach for such patients is the use of extracorporeal perfusion with porcine livers as a form of “liver dialysis”. During a 72-hour extracorporeal perfusion of porcine livers with human blood, porcine Kupffer cells bind to and phagocytose human red blood cells (hRBC) causing the hematocrit to decrease to 2.5% of the original value. Our laboratory has identified porcine sialoadhesin expressed on Kupffer cells as the lectin responsible for binding N-acetylneuraminic acid on the surface of the hRBC. We evaluated whether blocking porcine sialoadhesin prevents the recognition and subsequent destruction of hRBCs seen during extracorporeal porcine liver xenoperfusion. Ex vivo studies were performed using wild type pig livers perfused with isolated hRBCs for 72-hours in the presence of an anti-porcine sialoadhesin antibody or isotype control. The addition of an anti-porcine sialoadhesin antibody to an extracorporeal porcine liver xenoperfusion model reduces the loss of hRBC over a 72 hour period. Sustained liver function was demonstrated throughout the perfusion. This study illustrates the role of sialoadhesin in mediating the destruction of hRBCs in an extracorporeal porcine liver xenoperfusion model.
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