Graft-versus-Host Disease Causes Broad Suppression of Hematopoietic Primitive Cells and Blocks Megakaryocyte Differentiation in a Murine Model
Graft-versus-Host Disease Causes Broad Suppression of Hematopoietic Primitive Cells and Blocks Megakaryocyte Differentiation in a Murine Model
复制标题
移植物抗宿主病导致小鼠模型中造血原始细胞广泛抑制并阻碍巨核细胞分化
DOI：
10.1016/j.bbmt.2014.05.009
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发表时间：
2014-09-01
影响因子：
4.3
通讯作者：
Wang, Jianmin
中科院分区：
文献类型：
--
作者：
Lin, Yan;Hu, Xiaoxia;Wang, Jianmin
急性移植物抗宿主病（aGVHD）的血细胞减少和延迟的免疫重建表明预后不良。然而，供体来源的细胞造血在aGVHD中是如何受损的尚不清楚。我们通过研究单倍型MHC配型小鼠骨髓移植的aGVHD模型中造血动力学和造血干细胞及祖细胞的功能来解决这个问题。尽管造血在aGVHD期间被逐渐抑制，但供体来源的造血干细胞的造血再生潜力保持完整。原始造血细胞急剧减少，这些细胞产生普通髓系祖细胞（CMP）和巨核细胞/红细胞祖细胞（MEP）的能力缺陷。观察到这些效应沿着粒细胞/巨噬细胞祖细胞的增加，表明分化成MEP在aGVHD期间被阻断。有趣的是，环孢素A能够部分逆转造血抑制以及CMP的分化阻断。这些数据为aGVHD的发病机制提供了新的见解，并可能改善aGVHD的临床管理。(C)2014年美国血液和骨髓移植协会。
Cytopenia and delayed immune reconstitution with acute graft-versus-host disease (aGVHD) indicate a poor prognosis. However, how donor-derived cell hematopoiesis is impaired in aGVHD is not well understood. We addressed this issue by studying the kinetics of hematopoiesis and the functions of hematopoietic stem and progenitor cells in an aGVHD model with haplo-MHC-matched murine bone marrow transplantation. Although hematopoiesis was progressively suppressed during aGVHD, the hematopoietic regenerative potential of donor-derived hematopoietic stem cells remains intact. There was a dramatic reduction in primitive hematopoietic cells and a defect in the ability of these cells to generate common myeloid progenitors (CMPs) and megakaryocyte/erythrocyte progenitors (MEPs). These effects were observed along with a concomitant increase in granulocyte/macrophage progenitors, suggesting that differentiation into MEPs is blocked during aGVHD. Interestingly, cyclosporine A was able to partially reverse the hematopoietic suppression as well as the differentiation blockage of CMPs. These data provide new insights into the pathogenesis of aGVHD and may improve the clinical management of aGVHD. (C) 2014 American Society for Blood and Marrow Transplantation.