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学科主题: 临床医学
题名:
Allogeneic compact bone-derived mesenchymal stem cell transplantation increases survival of mice exposed to lethal total body irradiation: a potential immunological mechanism
作者: 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
发表日期: 2014-02-05
DOI: 10.3760/cma.j.issn.0366-6999.20132001
卷: 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
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
项目资助者: National Natural Science Foundation of China
WOS记录号: WOS:000333498400014
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/60328
Appears in Collections:北京大学第一临床医学院_血液内科_期刊论文

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作者单位: Peking Univ, Dept Hematol, Hosp 1, Beijing 100034, Peoples R China

Recommended Citation:
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.
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