Qiao Jianlin, Qi Kunming, Chu Peipei, Mi Hongling, Yang Na, Yao Haina, Xia Yuan, Li Zhenyu, Xu Kailin, Zeng Lingyu
Blood Diseases Institute, Xuzhou Medical College, Xuzhou, 221002, China.
Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou, 221002, China.
Liver Int. 2015 Dec;35(12):2611-20. doi: 10.1111/liv.12849. Epub 2015 Apr 28.
BACKGROUND & AIMS: Injury to liver sinusoidal endothelial cells (LSECs) is thought to be the initial factor for Hepatic veno-occlusive 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.
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-α and platelet activation.
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-α 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.
EPCs infusion ameliorated the damage to LSECs and hepatocytes as well as reduced secretion of IL-6, TNF-α 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.
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的起始因素。内皮祖细胞（EPCs）具有分化为内皮细胞的能力，在血管生成、组织再生和修复中起关键作用。EPCs输注是否能改善LSECs损伤尚不清楚。本研究旨在评估EPCs对HSCT后小鼠肝损伤的影响。
小鼠接受HSCT，分为未输注EPCs组（HSCT组）和输注EPCs组（HSCT + EPCs组）。未处理的小鼠作为对照。HSCT后采集肝脏和全血，用于分析肝窦内皮细胞（LSECs）和肝细胞的病理学、肝脏超微结构、功能、白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）水平及血小板活化情况。
HSCT组观察到严重的LSECs损伤、肝细胞损伤及肝功能异常。此外，还发现P-选择素表达增加以及IL-6、TNF-α分泌增多。然而，在所有时间点，上述所有变化在HSCT + EPCs组均得到缓解，并在终点时恢复正常。同时，添加抗血管内皮钙黏蛋白抗体可完全抑制EPCs诱导的LSECs和肝细胞修复。
EPCs输注改善了HSCT后LSECs和肝细胞的损伤，减少了IL-6、TNF-α的分泌，并抑制了血小板活化，从而改善了肝功能，提示EPCs可能是预防HSCT后肝损伤的一种新的治疗策略。
