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Allogeneic compact bone-derived mesenchymal stem cell transplantation increases survival of mice exposed to lethal total body irradiation: a potential immunological mechanism
Qiao Shukai; Ren Hanyun; Shi Yongjin; Liu Wei
关键词mesenchymal stem cells transplantation total body irradiation colony-forming unit granulocyte/macrophage immunological mechanism
刊名CHINESE MEDICAL JOURNAL
2014-02-05
DOI10.3760/cma.j.issn.0366-6999.20132001
127期:3页:475-482
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Medicine, General & Internal
资助者National Natural Science Foundation of China ; National Natural Science Foundation of China
研究领域[WOS]General & Internal Medicine
关键词[WOS]REGULATORY T-CELLS ; VERSUS-HOST-DISEASE ; HUMAN TRABECULAR BONE ; PROGENITOR CELLS ; IN-VITRO ; MARROW ; PROLIFERATION ; EXPRESSION ; INDUCTION ; RESPONSES
英文摘要

Background Radiation-induced injury after accidental or therapeutic total body exposure to ionizing radiation has serious pathophysiological consequences, and currently no effective therapy exists. This study was designed to investigate whether transplantation of allogeneic murine compact bone derived-mesenchymal stem cells (CB-MSCs) could improve the survival of mice exposed to lethal dosage total body irradiation (TBI), and to explore the potential immunoprotective role of MSCs.

Methods BALB/c mice were treated with 8 Gy TBI, and then some were administered CB-MSCs isolated from C57BL/6 mice. Survival rates and body weight were analyzed for 14 days post-irradiation. At three days post-irradiation, we evaluated IFN-gamma and IL-4 concentrations; CD4(+)CD25(+)Foxp3(+) regulatory T cell (Treg) percentage; CXCR3, CCR5, and CCR7 expressions on CD3(+) T cells; and splenocyte T-bet and GATA-3 mRNA levels. CB-MSC effects on bone marrow hemopoiesis were assessed via colony-forming unit granulocyte/macrophage (CFU-GM) assay.

Results After lethal TBI, compared to non-transplanted mice, CB-MSC-transplanted mice exhibited significantly increased survival, body weight, and CFU-GM counts of bone marrow cells (P<0.05), as well as higher Treg percentages, reduced IFN-gamma, CXCR3 and CCR5 down-regulation, and CCR7 up-regulation. CB-MSC transplantation suppressed Th1 immunity. Irradiated splenocytes directly suppressed CFU-GM formation from bone marrow cells, and CB-MSC co-culture reversed this inhibition.

Conclusion Allogeneic CB-MSC transplantation attenuated radiation-induced hematopoietic toxicity, and provided immunoprotection by alleviating lymphocyte-mediated CFU-GM inhibition, expanding Tregs, regulating T cell chemokine receptor expressions, and skewing the Th1/Th2 balance toward anti-inflammatory Th2 polarization.

语种英语
所属项目编号30940030 ; 81070448 ; 81370667
资助者National Natural Science Foundation of China ; National Natural Science Foundation of China
WOS记录号WOS:000333498400014
引用统计
被引频次:9[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/60328
专题北京大学第一临床医学院_血液内科
作者单位Peking Univ, Dept Hematol, Hosp 1, Beijing 100034, Peoples R China
推荐引用方式
GB/T 7714
Qiao Shukai,Ren Hanyun,Shi Yongjin,et al. Allogeneic compact bone-derived mesenchymal stem cell transplantation increases survival of mice exposed to lethal total body irradiation: a potential immunological mechanism[J]. CHINESE MEDICAL JOURNAL,2014,127(3):475-482.
APA Qiao Shukai,Ren Hanyun,Shi Yongjin,&Liu Wei.(2014).Allogeneic compact bone-derived mesenchymal stem cell transplantation increases survival of mice exposed to lethal total body irradiation: a potential immunological mechanism.CHINESE MEDICAL JOURNAL,127(3),475-482.
MLA Qiao Shukai,et al."Allogeneic compact bone-derived mesenchymal stem cell transplantation increases survival of mice exposed to lethal total body irradiation: a potential immunological mechanism".CHINESE MEDICAL JOURNAL 127.3(2014):475-482.
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