N-acetyl-L-cysteine improves bone marrow endothelial progenitor cells in prolonged isolated thrombocytopenia patients post allogeneic hematopoietic stem cell transplantation
N-acetyl-L-cysteine improves bone marrow endothelial progenitor cells in prolonged isolated thrombocytopenia patients post allogeneic hematopoietic stem cell transplantation
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N-乙酰-L-半胱氨酸可改善同种异体造血干细胞移植后长期孤立性血小板减少症患者的骨髓内皮祖细胞
DOI：
10.1002/ajh.25056
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发表时间：
2018-07-01
影响因子：
12.8
通讯作者：
Huang, Xiao-Jun
中科院分区：
文献类型：
--
作者：
Kong, Yuan;Shi, Min-Min;Huang, Xiao-Jun
长期孤立性血小板减少症（PT）是异基因造血干细胞移植（allo-HSCT）后的严重并发症。根据小鼠研究，内皮祖细胞（EPC）在骨髓（BM）微环境中造血和血小板生成的调节中发挥着至关重要的作用。我们之前表明，BM EPC 频率降低是异基因 HSCT 后发生 PT 的独立危险因素。然而，BM EPCs 的功能作用以及改善 PT 患者受损的 BM EPCs 的方法尚不清楚。在当前的病例对照研究中，我们研究了 PT 患者的 BM EPC 是否与移植功能良好的患者不同。此外，我们还评估了 N-乙酰基-L-半胱氨酸（NAC，一种活性氧 [ROS] 清除剂）是否可以在体外和体内增强 PT 患者的 BM EPC。 PT 患者表现出功能失调的 BM EPC，其特征是高水平的 ROS 和细胞凋亡以及迁移和血管生成能力下降。 NAC的体外治疗通过下调p38 MAPK途径改善了从PT患者培养的BM EPC的数量和功能，并挽救受损的BM EPC以支持巨核细胞生成。此外，根据初步临床研究结果，NAC对于PT患者是安全有效的。总之，这些结果表明，BM EPC 的减少和功能障碍与 PT 的发生有关。 NAC可以在数量和功能上改善PT患者中缺陷的BM EPC，这表明NAC是allo-HSCT后PT患者的一种有前途的治疗方法。
Prolonged isolated thrombocytopenia (PT) is a serious complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). According to murine studies, endothelial progenitor cells (EPCs) play a crucial role in the regulation of hematopoiesis and thrombopoiesis in the bone marrow (BM) microenvironment. We previously showed that the reduced frequency of BM EPCs was an independent risk factor for the occurrence of PT following allo-HSCT. However, the functional role of BM EPCs and methods to improve the impaired BM EPCs in PT patients are unknown. In the current case-control study, we investigated whether the BM EPCs in PT patients differed from those in good graft function patients. Moreover, we evaluated whether N-acetyl-L-cysteine (NAC, a reactive oxygen species [ROS] scavenger) could enhance BM EPCs from PT patients in vitro and in vivo. The PT patients exhibited dysfunctional BM EPCs characterized by high levels of ROS and apoptosis and decreased migration and angiogenesis capabilities. In vitro treatment with NAC improved the quantity and function of the BM EPCs cultivated from the PT patients by downregulating the p38 MAPK pathway and rescued the impaired BM EPCs to support megakaryocytopoiesis. Furthermore, according to the results of a preliminary clinical study, NAC is safe and effective in PT patients. In summary, these results suggested that the reduced and dysfunctional BM EPCs are involved in the occurrence of PT. The defective BM EPCs in the PT patients can be quantitatively and functionally improved by NAC, indicating that NAC is a promising therapeutic approach for PT patients following allo-HSCT.