Allogeneic compact bone-derived mesenchymal stem cell transplantation increases survival of mice exposed to lethal total body irradiation: a potential immunological mechanism

Allogeneic compact bone-derived mesenchymal stem cell transplantation increases survival of mice exposed to lethal total body irradiation: a potential immunological mechanism
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同种异体致密骨源间充质干细胞移植可提高遭受致命全身辐射的小鼠的存活率:一种潜在的免疫机制

DOI:
10.3760/cma.j.issn.0366-6999.20132001
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发表时间:
2014-02-05
影响因子:
6.1
通讯作者:
Liu Wei
Liu Wei
中科院分区:
医学2区
文献类型:
--
作者:
Qiao Shukai;Ren Hanyun;Liu Wei

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背景:电离辐射全身照射或治疗性照射后的辐射损伤具有严重的病理生理后果,目前尚无有效的治疗方法。本研究旨在观察同种异体小鼠密质骨源性间充质干细胞(CB-MSCs)移植能否提高致死剂量全身照射(TBI)小鼠的存活率,并探讨MSCs的潜在免疫保护作用。照射后14天分析存活率和体重。在照射后3天,我们评估IFN-γ和IL-4浓度; CD 4(+)CD 25(+)Foxp 3(+)调节性T细胞(Treg)百分比; CD 3(+)T细胞上CXCR 3、CCR 5和CCR 7表达;以及脾细胞T-bet和加塔-3 mRNA水平。结果与未移植小鼠相比,CB-MSC移植小鼠的存活率、体重和骨髓CFU-GM计数均显著增加(P < 0.05),骨髓CFU-GM计数也显著增加(P < 0.05)。
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