Iron overload as a risk factor for poor graft function following allogeneic hematopoietic stem cell transplantation

Iron overload as a risk factor for poor graft function following allogeneic hematopoietic stem cell transplantation
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铁过载是异基因造血干细胞移植后移植物功能不良的危险因素

DOI:
10.1002/kjm2.12238
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发表时间:
2020-07
影响因子:
3.3
通讯作者:
T
T
中科院分区:
医学4区
文献类型:
--
作者:
Xue-Qiong Wu;Kangni Lin;Minmin Chen;Peifang Jiang;Yuxin Zhang;Yongquan Chen;Qiuru Chen;Min Xiao;Haojie Zhu;Hajji Ally Issa;Shaozhen Chen;Xiaofeng Luo;Jinhua Ren;Qian Li;Yan-Ling Zeng;Jingjing Xu;Yi-Feng Lin;Rong Zheng;Zhihong Zheng;Zhizhe Chen;Ji;a Hu;T

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越来越多的血液恶性肿瘤采用异基因造血干细胞移植(allo-HSCT)进行治疗。不幸的是,铁过载是allo-HSCT的常见不良反应,并与预后不良相关。在本研究中,我们研究了铁超载小鼠的造血功能,并阐明了铁超载对骨髓(BM)微环境的影响。通过腹腔注射20 mg/mL糖化氧化铁产生铁过载BALB/C小鼠。进行苏木精-伊红染色以评价铁过载对小鼠的影响。通过尾静脉注射将从C57 BL/6小鼠获得的BM细胞移植到经照射的BALB/C小鼠(全身照射4戈伊,两次,间隔4小时)中。allo-HSCT后2周,通过集落形成试验评估受者的造血重建能力。组织学检查显示,从接受高剂量糖化氧化铁(20 mg/mL)注射的小鼠中收集的肝组织中存在棕色染色的颗粒状沉积物、排列不规则的淋巴细胞和BM中的蓝色染色块。铁负荷组小鼠血小板、血红蛋白(HGB)含量明显高于健康组,粒-巨噬细胞集落形成单位(CFU-GM)、红细胞集落形成单位(CFU-E)及粒-红-单核-巨核混合集落形成单位(CFU-mix)数量明显低于健康组。与健康受者相比,铁超负荷受者外周血中红细胞和HGB浓度降低,骨髓基质细胞、CFU-GM、CFU-E和CFU-mix沿着降低。综上所述,我们的研究结果表明,铁超载可能通过破坏骨髓微环境来改变小鼠移植后红细胞的数量,从而影响骨髓造血功能的恢复。
Hematological malignancies are increasingly treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT). Unfortunately, iron overload is a frequent adverse effect of allo-HSCT and is associated with poor prognosis. In the present study, we investigated hematopoiesis in iron-overloaded mice and elucidated the effects of iron overload on the bone marrow (BM) microenvironment. Iron-overloaded BALB/C mice were generated by injecting 20 mg/mL saccharated iron oxide intraperitoneally. Hematoxylin-eosin staining was performed to evaluate the effects of an iron overload in mice. BM cells obtained from C57BL/6 mice were transplanted into irradiated BALB/C mice (whole-body irradiation of 4 Gy, twice with a 4-hours interval) by tail vein injection. Two weeks after allo-HSCT, the hematopoietic reconstitution capacity was evaluated in recipients by colony-forming assays. Histopathological examinations showed brown-stained granular deposits, irregularly arranged lymphocytes in the liver tissues, and blue-stained blocks in the BM collected from mice received injections of high-dose saccharated iron oxide (20 mg/mL). Iron-overloaded mice showed more platelets, higher-hemoglobin (HGB) concentration, fewer granulocyte-macrophage colony-forming units (CFU-GM), erythrocyte colony-forming units (CFU-E), and mixed granulocyte/erythrocyte/monocyte/megakaryocyte colony-forming units (CFU-mix) than healthy mice. Iron-overloaded recipients presented with reduced erythrocytes and HGB concentration in peripheral blood, along with decreased marrow stroma cells, CFU-GM, CFU-E, and CFU-mix relative to healthy recipients. Taken together, our findings demonstrate that iron overload might alter the number of red blood cells after transplantation in mice by destroying the BM microenvironment, thereby affecting the recovery of BM hematopoietic function.
DOI: --
发表时间: 1999
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影响因子: 10.1
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发表时间: 2013-04-01
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发表时间: 2014-08-01
影响因子: 3.1
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