小鼠IL－3 cDNA转化细胞移植体内表达的初步研究

随着基因治疗技术的发展和多个细胞因子基因的克隆，人们提出了供细胞因子的基因治疗的设想，以期为肿瘤、老年性痴呆、严重的造血功能障碍等这样一类难治疾病的治疗另辟蹊径。为改善放射损伤小鼠受抑制的造血功能，我们采用基因治疗的方法，将小鼠ＩＬ－３基因ｃＤＮＡ与逆转录病毒载体重组，转染包装细胞ＰＡ３１７，用其分泌的含ＩＬ－３ｃＤＮＡ的复制缺陷逆转录病毒感染、转化ＮＩＨ３Ｔ３细胞，从中筛选可在体外分泌ＩＬ－３的克隆，将可分泌ＩＬ－３的细胞种植到放射损伤小鼠体内后发现：受体小鼠血清中检出了ＩＬ－３的活性；其外周血白细胞计数升至５５万／ｍｍ３，以成熟中性粒细胞为主；肝、脾脏内有大量各个分化阶段的中性粒细胞。这些结果表明：可以利用基因治疗技术，在体内表达ＩＬ－３，改善机体的造血功能。

Gene therapy:in vivo effects of 3T3 cells which were transformed with recombinant retrovirus carrying murine IL-3 cDNA

A Fibroblast-mediated gene delivery method was used for the endogenous expression of murine IL-3 as a model of cytokine gene supplement therapy.Murine IL-3 cDNA was inserted into the retroviral vecto LXSN,Using this vector and a help virus free system,a murine IL-3 producing cell line was established by infecting NIH/3T3 fibroblast cell with recombinant retroviruses carrying mIL-3 cDNA. The infected cells produced a consiberable amount of mIL-3.After the implantation of the IL-3 producing cells into normal BABL/c mice as well as irradiated mice,prominent neutrophilia was observed,moreover,the hematopoietic progenitor appeared in the livers and increased remarkably in the spleens of these mice.