移植GM—CSF基因修饰的骨髓细胞对小鼠造血恢复的影响

探索粒-巨噬细胞集落刺激因子(GM-CSF)基因修饰的骨髓细胞促进照射鼠骨髓移植后造血功能恢复的可行性。通过基因转移造血细胞进行骨髓移植的小鼠模型动态观察移植鼠外周血细胞数量、肝脾及骨髓形态学,CFU-S,CFU-GM及血清GM-CSF活性的变化。结果表明,实验组小鼠外周血白细胞与中性粒细胞计数,CFU-S及脾脏CFU-GM明显高于对照组(P<0.05),而各组间骨髓CFU-GM计数无显著性差异(P>0.05);组织学显示实验小鼠肝脾造血组织明显增多,而各组间骨髓象改变不大,并且血清GM-CSF活性也较对照组明显升高(P<0.01)。结论提示,给γ射线照射小鼠移植GM-CSF基因修饰的骨髓造血细胞能显著加快造血恢复的过程。

Effects of Transplantation with GM-CSF Gene Modified Bone Marrow Cells on Hematopoietic Recovery in Mice

In order to explore the feasibility for acceleration of hematopoietic recovery after bone manow transplantation by marrow cells modified with gene of GM-CSF, murine GM-CSF cDNA recombinant retrovirus pLXSN/ GM-CSF containg bacterial NeoR gene was transferred into retrovirus-packaging cell line PA317 by electropora-tion and supernatant of cultured G418 resistant clones was used to infect fresh bone marrow cells (BMCs) harvested from 5-FU-treated mice, and then the BMCs were transplanted into lethally irradiated syngeneic BALB/c mice. The BALB/c mice were established to constitutively produce GM-CSF by transplantation with 5-FU-treated syngeneic marrow cells infected with retroviral vectors bearing GM-CSF cDNA. Experimental results showed that the counts of ANC and WBC in peripheral blood and the numbers of CFU-S and CFU-GM in spleen were significantly enhanced in mice transplanted with GM-CSF viral-infected marrow cells (GM-CSF group), whereas no significant differences in CFU-GM derived from marrow cells were observed bet ween any two of the groups. Histological observation of spleen and liver in recipient mice showed that the hematopoietic foci appeared in the liver and increased remarkably in the spleen in GM-CSF group. It was concluded that the hematopoietic cells modified with GM-CSF gene could accelerate recovery of hematopoietic suppression after bone marrow transplantation.