Ex vivo perfusion of human spleens maintains clearing and processing functions
Ex vivo perfusion of human spleens maintains clearing and processing functions
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DOI：
10.1182/blood-2005-10-4094
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发表时间：
2006-05-01
期刊：
影响因子：
20.3
通讯作者：
David, PH
中科院分区：
文献类型：
--
作者：
Buffet, PA;Milon, G;David, PH
脾脏在几种潜在的严重疾病的病理生理学中起着核心作用，如遗传性红细胞膜疾病、溶血性贫血和疟疾。对这些疾病的研究受到限制人类脾脏组织探索的伦理约束的阻碍。我们确定了一种手术情况-对取出的完整脾脏进行体外灌注4至6小时，可维持保留的实质结构、血管流量和代谢活性。通过测试分离灌注的脾脏保留预先暴露于抗疟药物青蒿琥酯（Art-iRBC）的恶性疟原虫感染的红细胞的能力来评估功能保留。超过95%的Art-iRBC在2小时内从灌注液中清除。在每次通过隔离灌注的脾脏时，从0.2%至0.23%的Art-iRBC中清除了寄生虫残留，这一比例与先前在青蒿琥酯治疗患者中确定的0.02%至1%的点蚀率一致。组织学分析显示，超过90%的Art-iRBC在红髓中保留和加工，这提供了人类脾脏清除区域依赖性寄生虫的第一个直接证据。现在可以在人体组织背景下实验性地探索涉及脾脏的清除或处理功能的人类特异性生理或病理生理机制。
The spleen plays a central role in the pathophysiology of several potentially severe diseases such as inherited red cell membrane disorders, hemolytic anemias, and malaria. Research on these diseases is hampered by ethical constraints that limit human spleen tissue explorations. We identified a surgical situation-left splenopancreatectomy for benign pancreas tumors-allowing spleen retrieval at no risk for patients. Ex vivo perfusion of retrieved intact spleens for 4 to 6 hours maintained a preserved parenchymal structure, vascular flow, and metabolic activity. Function preservation was assessed by testing the ability of isolated-perfused spleens to retain Plasmodium falciparum-infected erythrocytes preexposed to the antimalarial drug artesunate (Art-iRBCs). More than 95% of Art-iRBCs were cleared from the perfusate in 2 hours. At each transit through isolated-perfused spleens, parasite remnants were removed from 0.2% to 0.23% of Art-iRBCs, a proportion consistent with the 0.02% to 1% pitting rate previously established in artesunate-treated patients. Histologic analysis showed that more than 90% of Art-iRBCs were retained and processed in the red pulp, providing the first direct evidence of a zone-dependent parasite clearance by the human spleen. Human-specific physiologic or pathophysiologic mechanisms involving clearing or processing functions of the spleen can now be experimentally explored in a human tissue context.