Impairment of bone marrow endothelial progenitor cells in acute graft-versus-host disease patients after allotransplant
Impairment of bone marrow endothelial progenitor cells in acute graft-versus-host disease patients after allotransplant
复制标题
同种异体移植后急性移植物抗宿主病患者骨髓内皮祖细胞的损伤
DOI：
10.1111/bjh.15456
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发表时间：
2018-09-01
影响因子：
6.5
通讯作者：
Huang, Xiao-Jun
中科院分区：
文献类型：
--
作者：
Cao, Xie-Na;Kong, Yuan;Huang, Xiao-Jun
移植物抗宿主病(GVHD)是异基因造血干细胞移植(allo-HSCT)后的主要并发症，常与骨髓抑制相关，临床处理具有挑战性。骨髓内皮祖细胞在造血和血小板生成的调节中起着重要的作用。然而，关于骨髓内皮祖细胞在急性移植物抗宿主病(AGVHD)患者中的功能作用知之甚少。在目前的前瞻性病例对照研究中，与非aGVHD患者相比，aGVHD患者的骨髓内皮祖细胞减少和功能障碍，其特征是迁移和血管生成能力降低，活性氧物种(ROS)水平和细胞凋亡增加。此外，aGVHD患者的BM CD34(+)细胞的ROS、细胞凋亡和DNA损伤的频率和水平均低于无aGVHD患者，但集落形成单位的培养效率低于无aGVHD患者。AGVHD患者中aGVHD和GVHD介导的细胞减少的严重程度与骨髓EPC受损有关。此外，EPC损伤与ROS水平呈正相关。综上所述，我们的结果提示骨髓内皮祖细胞减少和功能障碍可能参与了aGVHD的发病机制。虽然这些发现还需要验证，但我们的数据表明，骨髓内皮祖细胞的改善可能代表着aGVHD患者一种有前途的治疗方法。
Graft-versus-host disease (GVHD) is a major complication after allogeneic haematopoietic stem cell transplantation (allo-HSCT) that is frequently associated with bone marrow (BM) suppression, and clinical management is challenging. BM endothelial progenitor cells (EPCs) play crucial roles in the regulation of haematopoiesis and thrombopoiesis. However, little is known regarding the functional roles of BM EPCs in acute GVHD (aGVHD) patients. In the current prospective case-control study, reduced and dysfunctional BM EPCs, characterized by decreased migration and angiogenesis capacities and increased levels of reactive oxygen species (ROS) and apoptosis, were found in aGVHD patients compared with those without aGVHD. Moreover, lower frequency and increased levels of ROS, apoptosis and DNA damage, but reduced colony-forming unit-plating efficiency were found in BM CD34(+) cells of aGVHD patients compared with those without aGVHD. The severity of aGVHD and GVHD-mediated cytopenia was associated with BM EPC impairment in aGVHD patients. In addition, the EPC impairment positively correlated with ROS level. Taken together, our results suggest that reduced and dysfunctional BM EPCs may be involved in the pathogenesis of aGVHD. Although these findings require validation, our data indicate that improvement of BM EPCs may represent a promising therapeutic approach for aGVHD patients.