Infusion of endothelial progenitor cells ameliorates liver injury in mice after haematopoietic stem cell transplantation
Infusion of endothelial progenitor cells ameliorates liver injury in mice after haematopoietic stem cell transplantation
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输注内皮祖细胞可改善造血干细胞移植后小鼠的肝损伤
DOI：
10.1111/liv.12849
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发表时间：
2015-12-01
影响因子：
6.7
通讯作者：
Zeng, Lingyu
中科院分区：
文献类型：
--
作者：
Qiao, Jianlin;Qi, Kunming;Zeng, Lingyu
背景和目标：肝窦内皮细胞（LSECs）损伤被认为是造血干细胞移植（HSCT）后严重并发症肝静脉闭塞病（Hepatic venoocclusive disease）的始动因素。内皮祖细胞（Endothelial progenitor cells，EPCs）具有向内皮细胞分化的能力，在血管生成、组织再生和修复中发挥重要作用。EPCs输注是否能改善LSEC损伤仍不清楚。本研究旨在探讨内皮祖细胞对小鼠造血干细胞移植后肝损伤的影响。方法：小鼠接受HSCT + EPCs（HSCT + EPCs）或不输注EPCs（HSCT + EPCs）。未处理的小鼠用作对照。HSCT后采集肝脏和全血，用于肝窦内皮细胞（LSECs）和肝细胞的病理学、肝脏超微结构、功能、IL-6、TNF-α水平和血小板活化的分析。结果：HSCT组出现严重的LSEC损伤、肝细胞损伤、肝功能异常。HSCT + EPCs组P-selectin的表达及IL-6、TNF-α的分泌在各时间点均较对照组明显降低，至治疗结束时恢复正常。同时，EPCs诱导的LSEC和肝细胞的修复被抗VE-钙粘蛋白抗体完全抑制。结论：EPCs可减轻HSCT后LSEC和肝细胞的损伤，减少IL-6、TNF-α的分泌，抑制血小板活化，改善肝功能，提示EPCs可能是预防HSCT后肝损伤的一种新的治疗策略。
Background & Aims: Injury to liver sinusoidal endothelial cells (LSECs) is thought to be the initial factor for Hepatic venoocclusive disease, a severe complication after haematopoietic stem cell transplantation (HSCT). Endothelial progenitor cells (EPCs) have the capacity to differentiate into endothelial cells and play a critical role in vasculogenesis, tissue regeneration and repair. Whether EPCs infusion ameliorates LSECs injury remains unclear. The aim of this study was to evaluate the effects of EPCs on liver injury in mice after HSCT. Methods: Mice received HSCT without or with EPCs infusion (HSCT + EPCs). Untreated mice were used as control. Liver and whole blood were collected post HSCT and used for the analysis of pathology of liver sinusoidal endothelial cells (LSECs) and hepatocytes, liver ultrastructure, function, level of IL-6, TNF-alpha and platelet activation. Results: Severe LSECs injury, hepatocyte damage, abnormal liver function was observed in HSCT group. In addition, increased P-selectin expression and secretion of IL-6, TNF-alpha was also found. However, all the above changes were alleviated in HSCT + EPCs at all the time points and normalized at the endpoint. Meanwhile, EPCs-induced repair of LSECs and hepatocytes was totally inhibited by the addition of anti-VE-cadherin antibody. Conclusions: EPCs infusion ameliorated the damage to LSECs and hepatocytes as well as reduced secretion of IL-6, TNF-alpha and inhibited platelet activation after HSCT, leading to improved liver function, suggesting EPCs might be a new therapeutic strategy in the prophylaxis of liver injury after HSCT.