An extracorporeal blood-cleansing device for sepsis therapy
An extracorporeal blood-cleansing device for sepsis therapy
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DOI：
10.1038/nm.3640
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发表时间：
2014-10-01
期刊：
影响因子：
82.9
通讯作者：
Ingber, Donald E.
中科院分区：
文献类型：
--
作者：
Kang, Joo H.;Super, Michael;Ingber, Donald E.
在这里，我们描述了一种受脾启发而用于脓毒症治疗的血液净化装置，它可以连续清除血液中的病原体和毒素，而不需要首先识别感染源。从感染者流出的血液与包裹了一种经过改造的人调理甘露糖结合凝集素(MBL)的磁性纳米棒混合，这种凝集素可以捕获广泛的病原体和毒素，而不会激活补体因子或凝血。磁铁从血液中提取与调理素结合的病原体和毒素；然后将净化后的血液返回给患者。该生物胸膜在体外以每小时高达1.25升的速度有效地清除流经单个生物胸膜单元的全人类血液中的多种革兰氏阴性和革兰氏阳性细菌、真菌和内毒素。在感染金黄色葡萄球菌或大肠杆菌的大鼠中，生物多糖清除了血液中90%的细菌，减少了病原体和免疫细胞在多个器官的渗透，并降低了炎性细胞因子的水平。在内毒素休克模型中，生物多糖在治疗5小时后提高了存活率。
Here we describe a blood-cleansing device for sepsis therapy inspired by the spleen, which can continuously remove pathogens and toxins from blood without first identifying the infectious agent. Blood flowing from an infected individual is mixed with magnetic nanobeads coated with an engineered human opsonin mannose-binding lectin (MBL) that captures a broad range of pathogens and toxins without activating complement factors or coagulation. Magnets pull the opsonin-bound pathogens and toxins from the blood; the cleansed blood is then returned back to the individual. The biospleen efficiently removes multiple Gram-negative and Gram-positive bacteria, fungi and endotoxins from whole human blood flowing through a single biospleen unit at up to 1.25 liters per h in vitro. In rats infected with Staphylococcus aureus or Escherichia coli, the biospleen cleared >90% of bacteria from blood, reduced pathogen and immune cell infiltration in multiple organs and decreased inflammatory cytokine levels. In a model of endotoxemic shock, the biospleen increased survival rates after a 5-h treatment.