通过产生对甲氨蝶呤耐药的骨髓来保护骨髓移植受者免受致死剂量甲氨蝶呤的伤害。
Protection of bone marrow transplant recipients from lethal doses of methotrexate by the generation of methotrexate-resistant bone marrow.
作者信息
Williams D A, Hsieh K, DeSilva A, Mulligan R C
出版信息
J Exp Med. 1987 Jul 1;166(1):210-8. doi: 10.1084/jem.166.1.210.
Abstract
To develop a highly efficient means for generating methotrexate resistant (MTXr) hematopoietic cells in vivo, a recombinant retroviral genome was constructed that encodes a MTXr dihydrofolate reductase (DHFRr). Cell lines producing high titers of virus capable of transmitting the DHFR gene were generated and used to infect mammalian cells in vitro. Analysis of infected fibroblasts indicated that the DHFRr gene was transmitted intact and conferred a high level of MTXr upon cells. Based on these findings, DHFRr-containing virus was used to infect murine bone marrow cells in vitro. Following infection, the transduced cells were introduced into lethally irradiated recipients via bone marrow transplantation techniques. The presence of the proviral sequences in cells of the spleen and bone marrow of engrafted recipients was associated with significantly increased survival of mice treated with otherwise lethal doses of MTX.
摘要
为了开发一种在体内高效生成甲氨蝶呤抗性（MTXr）造血细胞的方法，构建了一种重组逆转录病毒基因组，该基因组编码一种MTXr二氢叶酸还原酶（DHFRr）。产生能够传递DHFR基因的高滴度病毒的细胞系被构建出来，并用于体外感染哺乳动物细胞。对感染的成纤维细胞的分析表明，DHFRr基因完整传递并赋予细胞高水平的MTXr。基于这些发现，含DHFRr的病毒被用于体外感染小鼠骨髓细胞。感染后，通过骨髓移植技术将转导的细胞引入接受致死剂量照射的受体。在移植受体的脾脏和骨髓细胞中存在前病毒序列与用致死剂量的MTX治疗的小鼠存活率显著提高相关。
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