Graft-versus-host disease causes broad suppression of hematopoietic primitive cells and blocks megakaryocyte differentiation in a murine model.
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.
Institute of Hematology, Changhai Hospital, Second Military Medical University, Shanghai, China.
Yan
Y
Lin
Institute of Hematology, Changhai Hospital, Second Military Medical University, Shanghai, China.
Xiaoxia
X
Hu
State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, and Center for Stem Cell Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.
Hui
H
Cheng
State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, and Center for Stem Cell Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.
Yakun
Y
Pang
Institute of Hematology, Changhai Hospital, Second Military Medical University, Shanghai, China.
Libing
L
Wang
Institute of Hematology, Changhai Hospital, Second Military Medical University, Shanghai, China.
Lin
L
Zou
Institute of Hematology, Changhai Hospital, Second Military Medical University, Shanghai, China.
Sheng
S
Xu
Institute of Hematology, Changhai Hospital, Second Military Medical University, Shanghai, China.
Xiaomeng
X
Zhuang
Institute of Hematology, Changhai Hospital, Second Military Medical University, Shanghai, China.
Chuanhe
C
Jiang
State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, and Center for Stem Cell Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.
Weiping
W
Yuan
State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, and Center for Stem Cell Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.
Tao
T
Cheng
Institute of Hematology, Changhai Hospital, Second Military Medical University, Shanghai, China. Electronic address: jmwangch@139.com.
Jianmin
J
Wang
D000818:Animals; D002454:Cell Differentiation; D006086:Graft vs Host Disease / Q000150:complications*; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D008533:Megakaryocytes / Q000166:cytology*; D051379:Mice; D023421:Models, Animal
Acute graft-versus-host disease; Cell cycle; Cyclosporine A; Hematopoietic progenitor cells; Hematopoietic stem cells