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Blocking tumor cell immune escape of leukemic mouse in bone marrow transplantation by transfection of soluble Fas gene
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- Author:
- No author available
- Journal Title:
- CHINESE JOURNAL OF ORGAN TRANSPLANTATION
- Issue:
- 7
- DOI:
- 10.3760/cma.j.issn.0254-1785.2006.07.005
- Key Word:
- 转染;肿瘤逃逸;骨髓移植;白血病
Abstract： 目的探讨骨髓细胞转染小鼠可溶性Fas(sFas)基因后移植能否阻抑白血病小鼠肿瘤细胞的免疫逃逸.方法用AdEasy系统构建携带sFas和EGFP的腺病毒质粒,先按病毒/细胞的感染倍数(MOI)为100的比例分别直接感染呈对数生长期的EL4细胞,培养24 h后,采用氚标记胸腺嘧啶掺入法检测其诱导YAC-1细胞凋亡的情况.然后同法以携带sFas和EGFP的腺病毒质粒分别转染雄性C57BL/6小鼠骨髓细胞,每只雌性C57BL/6小鼠(白血病模型)通过尾静脉接受5×106～10×106个转染sFas或EGFP的雄性C57BL/6小鼠骨髓单个核细胞移植.移植后观察受者的造血重建情况、白血病/淋巴瘤的发生及生存率.结果体外实验中,转染EGFP的EL4细胞诱导YAC-1细胞凋亡的情况与非转染的EL4细胞相似,转染sFas基因后,YAC-1细胞的凋亡率明显下降(P＜0.01).接受转染sFas基因的骨髓移植者,移植后8周受者全部存活(16/16),骨髓中未发现EL4细胞,造血功能恢复良好,能检测到Y染色体;接受转染EGFP的骨髓移植者,移植后8周仅1只小鼠(1/16)存活(P＜0.01),在死亡和存活的小鼠中均存在EL4细胞,其造血重建情况较转sFas者差.结论转染sFas基因的造血细胞移植可以在体内阻抑肿瘤细胞的免疫逃逸,同时不影响造血重建功能.
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