Zheng Yuling, Ran Ying, Wu Juan, Yang Ping, Liao Xinyi, Zhang Jie, Meng Wentong, Gou Daming, Li Li, Du Lei, Lin Jing
Department of Anesthesiology, West China Hospital, Sichuan University & West China Research Unit, Chinese Academy of Medical Sciences, Chengdu, Sichuan, 610041, People's Republic of China.
Department of Anesthesiology, Zunyi Maternal and Child Health Care Hospital, Zunyi, Guizhou, 563000, People's Republic of China.
J Inflamm Res. 2025 Apr 18;18:5355-5370. doi: 10.2147/JIR.S503575. eCollection 2025.
Cardiopulmonary bypass (CPB) is associated with activation of pro-inflammatory cells, which infiltrate tissues and cause injury. Here we explored a novel disposable remover to remove inflammatory leukocytes in order to reduce risk of complications after CPB. This is a substudy within a previously registered clinical trial (NCT05400356) that aims to validate a novel disposable remover to remove activated leukocytes generated during CPB.
The device contains an enhanced biocompatible leukocyte membrane (Chinese patent CN202310822538.X) coated with RGD peptide (Arg-Gly-Asp), which binds to specific polypeptide groups on activated leukocytes, leading to their affinity-based adsorption. The device was integrated into a closed extracorporeal circuit containing a blood reservoir, roller pump, and tubes. Blood from seven patients (150 mL per patient) was driven through the circuit for 10 min at 300 mL/min. Counts of leukocytes and their surface molecules were examined before circulation and after 2.5, 5, 7.5, and 10 min of circulation. The types and morphology of blood cells captured on the filter membrane were also examined.
Counts of neutrophils and neutrophils expressing the activation markers CD11b, CD54, CD64 or CD181 decreased rapidly by 36-39% during the first 2.5 min of circulation, after which their counts decreased more slowly. In contrast, counts of monocytes or lymphocytes did not change significantly during circulation. After use, the membrane was still smooth and intact, and it contained substantial numbers of intact activated leukocytes, based on immunostaining against activated cells and scanning electron microscopy. Smears of blood samples before and after circulation showed no significant differences in each leukocyte morphology.
This novel disposable remover can preferentially remove activated neutrophils from blood ex vivo, with minimal apparent impact on other leukocytes and blood components.
This substudy is part of a prospective cohort study registered at the Clinical Trials Registry (NCT05400356) on 27 May 2022.
体外循环（CPB）与促炎细胞的激活有关，这些细胞浸润组织并导致损伤。在此，我们探索了一种新型一次性去除装置，以去除炎性白细胞，从而降低CPB后并发症的风险。这是一项在先前注册的临床试验（NCT05400356）中的子研究，旨在验证一种新型一次性去除装置，以去除CPB期间产生的活化白细胞。
该装置包含一种增强型生物相容性白细胞膜（中国专利CN202310822538.X），表面涂有RGD肽（精氨酸-甘氨酸-天冬氨酸），该肽与活化白细胞上的特定多肽基团结合，从而实现基于亲和力的吸附。该装置被集成到一个包含储血器、滚压泵和管道的封闭体外循环回路中。将7名患者的血液（每位患者150 mL）以300 mL/min的速度驱动通过该回路10分钟。在循环前以及循环2.5、5、7.5和10分钟后检查白细胞及其表面分子的计数。还检查了滤膜上捕获的血细胞的类型和形态。
在循环的前2.5分钟内，中性粒细胞以及表达活化标志物CD11b、CD54、CD64或CD181的中性粒细胞计数迅速下降36%-39%，此后其计数下降得更慢。相比之下，单核细胞或淋巴细胞的计数在循环期间没有显著变化。使用后，膜仍然光滑完整，基于对活化细胞的免疫染色和扫描电子显微镜检查，膜上含有大量完整的活化白细胞。循环前后血样涂片显示各白细胞形态无显著差异。
这种新型一次性去除装置可以在体外优先从血液中去除活化的中性粒细胞，对其他白细胞和血液成分的明显影响最小。
该子研究是一项前瞻性队列研究的一部分，该研究于2022年5月27日在临床试验注册中心注册（NCT05400356）。
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