Ad/IFNγ转染的骨髓基质细胞的体内抗白血病作用

In vivo anti-leukemic effect BMSC transfected with adenovirus-mediated of gamma interferon gene

目的观察Ad/IFNγ转染的骨髓基质细胞在小鼠体内表达IFNγ的特征及规律,并观察其抗白血病作用。方法Ad/IFNγ(MOI=50,MOI感染复数)体外转染骨髓基质细胞,并通过RT-PCR,ELISA检测骨髓基质细胞表达IFNγ;将K562细胞成瘤的裸鼠随机分为3组,分别给予静脉回输Ad/IFNγ转染的骨髓基质细胞、Ad/LacZ转染的骨髓基质细胞以及未转染的骨髓基质细胞,每只裸鼠的回输量为2×106个细胞,以RT-PCR,ELISA检测IFNγ在裸鼠体内表达的规律并观察其抑瘤效应及生存期。结果RT-PCR,ELISA于体外均能检测到IFNγ的表达。体内研究发现,Ad/IFNγ-骨髓基质细胞组在体内检测到的IFNγ主要分布在肝、脾、骨髓和肿瘤中,但在血液中未能检测到IFNγ的表达。并且,Ad/IFNγ-骨髓基质细胞于体内有明显的抑瘤效应,并能够延长其生存期。结论骨髓基质细胞能够将外源性IFNγ基因携带至肝、脾、骨髓等造血组织,也能携带至肿瘤组织,基因修饰的骨髓基质细胞为我们提供了治疗白血病的新的前景。

Objective To study the characteristics of IFNγ expression by BMSC transfected with adenovirusmediated gamma interferon gene in nude mice and its anti- leukemic effect in vivo. Methods BMSC was transfected by Ad/IFNγ at a MOI of 50. RT- PCR and EKISA was used to examine the expression of IFN - γ. Mice with K562 - derived tumor were random- ized into three groups injected with：BMSC of Ad/IFNγ, BMSC with Ad/lacZ or BMSC. BMSC was given at 2× 10^6/per mouse by tail vein. The expressions of IFNγ mRNA and protein were examined, and suvival time of mice was studied. Result IFNγ could be detected in vitro and in vivo. Adenovirus - mediated gamma interferon gene tranfeeted BMSC mainly distributed in the liver, spleen, bone marrow and within the tumor, but IFNγ was not detected in the blood. Adenvovims - mediated gamma interferon gene transfected BMSC showed anti - leukemic effects and prolonged the suvival time of mice. Conehisions BMSC can conduct exogenous gene into the live, spleen, bone marrow and other hematopoietic tissue,and the tumor tissue. Gene-medified BMSC is a promising therapy for the treatment of malignancy.