Macrophages ameliorate bone marrow inflammatory injury and promote hematopoiesis in mice following hematopoietic stem cell transplantation
Macrophages ameliorate bone marrow inflammatory injury and promote hematopoiesis in mice following hematopoietic stem cell transplantation
复制标题
巨噬细胞改善造血干细胞移植后小鼠骨髓炎症损伤并促进造血
DOI：
10.3892/etm.2018.6209
复制
发表时间：
2018-08-01
影响因子：
2.7
通讯作者：
Zeng, Lingyu
中科院分区：
文献类型：
--
作者：
Qiao, Jianlin;Liu, Lu;Zeng, Lingyu
骨髓巨噬细胞已被证明在促进造血干细胞 (HSC) 的维持和保留方面发挥着关键作用。我们之前的研究表明造血干细胞移植（HSCT）后骨髓中巨噬细胞浸润增加。然而，目前尚不清楚巨噬细胞是否影响HSCT后的造血重建。本研究旨在探讨巨噬细胞在HSCT后造血重建中的作用。将BALB/c小鼠分为HSCT组、HSCT+氯膦酸盐脂质体组、HSCT+PBS脂质体组、HSCT+RS102895组和HSCT+载体组，并在HSCT后第7、14、21、28和35天处死。通过H&E染色分析检测骨髓病理变化，并通过免疫组织化学染色和蛋白质印迹分析评估巨噬细胞的数量。通过流式细胞术测量c-kit+sca-1+和c-kit+的数量。骨髓巨噬细胞耗竭的小鼠表现出总体存活率显着降低、造血恢复延迟、造血干/祖细胞和骨髓细胞数量减少以及骨髓损伤加剧。然而，与HSCT+Vehicle组相比，骨髓巨噬细胞数量增加的小鼠总体存活率没有差异，造血重建加速，造血干/祖细胞和骨髓细胞数量增多，骨髓损伤得到改善。总之，本研究表明骨髓巨噬细胞在骨髓损伤中发挥保护作用，并可能促进造血干细胞移植后小鼠的造血功能，这表明操纵巨噬细胞可能是提高造血干细胞移植疗效的新策略。
Bone marrow macrophages have been demonstrated to serve a critical role in promoting maintenance and retention of hematopoietic stem cells (HSCs). Our previous study indicated increased macrophages infiltration in bone marrow after HSC transplantation (HSCT). However, it is not well understood whether macrophages affect hematopoietic reconstitution after HSCT. The present study aimed to investigate the role of macrophages in hematopoietic reconstitution after HSCT. BALB/c mice were divided into HSCT, HSCT+Clodronate Liposomes, HSCT+PBS Liposomes, HSCT+RS102895 and HSCT+Vehicle groups and sacrificed on day 7, 14, 21, 28 and 35 after HSCT. Analysis was performed to detect the changes of bone marrow pathology by H&E staining and the number of macrophages was assessed by immunohistochemical staining and western blot analysis. The number of c-kit+sca-1+ and c-kit+ was measured by flow cytometry. Mice with a depletion of bone marrow macrophages displayed significantly reduced overall survival, delayed hematopoietic recovery, a reduced number of hematopoietic stem/progenitor cells and bone marrow cells as well as exaggerated bone marrow injury. However, compared with the HSCT+Vehicle group, mice with an increased number of bone marrow macrophages exhibited no difference of overall survival, had accelerated hematopoietic reconstitution, a higher number of hematopoietic stem/progenitor cells and bone marrow cells and ameliorated bone marrow injury. In conclusion, the present study indicated that bone marrow macrophages serve a protective role in bone marrow injury and may promote hematopoiesis in mice after HSCT, suggesting manipulation of macrophages may be a novel strategy for improving the efficacy of HSCT.