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骨髓间质干细胞降低大鼠移植物抗宿主反应的实验研究

Bone marrow-derived mesenchymal stem cells decreases rats’ graft-versus-host disease after allogeneic hematopoietic stem cells transplantation

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【作者】 田莹邓宇斌王亚柱王晔朱文标

【Author】 TIAN Ying,DENG Yu-bin,WANG Ya-zhu,WANG Ye,ZHU Wen-biao(Cancer Center,Sun Yat-Sen University,Guangzhou,510060,China)

【机构】 中山大学医学院病理生理学教研室中山大学医学院病理生理学教研室 广州510060广州510060

【摘要】 目的探讨MSCs对GVHD的作用及其机制。方法建立大鼠同种异体骨髓移植模型,同时输入供者的T淋巴细胞诱导出移植物抗宿主反应,联合或不联合移植供体来源的MSCs,观察受鼠的生存时间,同时利用RT-PCR法研究Th1/Th2淋巴细胞亚群的比例,用ELISA法检测移植后体内IL-4细胞因子的浓度。结果GVHD组的平均生存时间为(17.30±2.33)天,实验组的平均生存时间为(24.10±2.36)天,与单独移植HSCs相比,MSCs与HSCs共移植明显延长的受鼠的生存时间。同时,GVHD组Th1/Th2细胞比值为1.29±0.06,IL-4因子的浓度平均为(14.84±2.59)pg/mL,实验组Th1/Th2细胞比值为(0.77±0.14),IL-4因子的浓度平均为(40.09±13.99)pg/mL。MSCs与HSCs共移植降低了体内Th1/Th2淋巴细胞亚群的比例,提高了体内IL-4细胞因子的浓度。结论MSCs与HSCs共移植能有效抑制HSCs移植后致死性GVHD的发生,延长生存时间,同时MSCs可能通过作用于体内Th1/Th2淋巴细胞亚群的比例,促进体内IL-4细胞因子的分泌从而间接发挥了抑制GVHD的作用。

【Abstract】 Objective To investigate the effects of bone marrow-derived mesenchymal stem cells(MSCs)on graft-versus-host disease(GVHD)after allogeneic hematopoietic stem cells transplantation(allo-HSCT)and the mechanisms.Methods The rat model of GVHD has been established by allogeneic HSCs with donor-derived T cells,with or without donor-derived MSCs co-transplantation.Effects of MSCs on GVHD were analyzed by median survival time of model rats.Ratio of Th1/Th2 T cells was assessed by RT-PCR and the concentration of IL-4 cytokine was assessed by ELISA.Results MSCs inhibited the lethal GVHD and increased the rats’ survival time after allo-HSCT.The median survival time was(17.30±2.33)d and 924.10±2.36)d in GVHD and experimental groups,respectively.Meantime,the ratio of Th1/Th2 T cells was 1.29±0.06 and 0.77±0.14 and the concentration of IL-4 cytokine was(14.84±2.59)pg/mL and(40.09±13.99)pg/mL in GVHD and experimental groups,respectively.The ratio of Th1/Th2 T cells was lower and the concentration of IL-4 cytokine was higher in experimental group than those in GVHD group.Conclusion MSCs may prevent the lethal GVHD after allo-HSCT by through Th1/Th2 T cells in vivo.

【基金】 广东省科技计划资助项目(2005B50301012)
  • 【文献出处】 免疫学杂志 ,Immunological Journal , 编辑部邮箱 ,2008年01期
  • 【分类号】R457.7
  • 【被引频次】48
  • 【下载频次】206
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