HGF基因修饰增强间充质干细胞的免疫抑制作用  

Hepatocyte growth factor gene modification enhancing immunosuppressive activity of human bone marrow-derived mesenchymal stem cells

作　　者：边莉[1] 郭子宽[1] 艾辉胜[2] 王华[1] 孟二红[1] 吴祖泽[1] 王立生[1] 

机构地区：[1]军事医学科学院放射与辐射医学研究所,北京100850 [2]军事医学科学院附属医院血液科,北京100071

出　　处：《军事医学科学院院刊》2006年第4期323-328,共6页Bulletin of the Academy of Military Medical Sciences

基　　金：国家自然科学基金项目(30370528;30400182)

摘　　要：目的:探讨HGF基因在间充质干细胞(m esenchym al stem cell,MSC)中过表达对细胞生物学的影响,为扩充MSC临床应用范围提供依据。方法:用携带HGF基因的重组腺病毒感染人骨髓来源的间充质干细胞后,与对照细胞相比,进行以下项目的检测:FCM测定细胞表型;MTT法测定细胞增殖能力;ALP和钙定量以及组织化学染色检测细胞体外成骨和成脂肪能力;3H-TdR掺入法测定MSC-HGF对混合淋巴细胞反应中效应细胞增殖活性的抑制作用。结果:HGF基因转染后MSC表型、体外增殖和分化能力无改变;混合淋巴细胞反应中,MSC-HGF对异基因抗原诱导的淋巴细胞增殖活性的抑制效应存在剂量依赖关系;MSC-HGF/MSC与效应细胞比例为1∶80时,MSC组淋巴细胞增殖活性(cpm值)降低19.8%,MSC-HGF组降低68.3%,抑制率是MSC组的3.45倍。结论:HGF基因转染的人骨髓MSC仍维持固有的增殖和分化能力,而对体外细胞免疫反应具有更强的抑制效果,提示MSC-HGF在造血干细胞移植和器官移植中的潜在应用价值。Objective ： To explore the effect of over-expression of hepatocyte growth factor （HGF） gene in mesenchymal stem cell（MSC） on cell biology in order to provide a basis for novel clinical use of MSC. Methods： The phenotype was assessed by flow cytometric analysis and cell proliferation was determined by MTr test. In vitro differentiation of MSC into osteoblasts and adipoblasts was evaluated by lineage-specific histochemical staining. Furthermore, the inhibitory effect of MSC-HGF on lymphocyte proliferation in mixed lymphocyte reaction was determined by ^3H-TdR incorporation assay. Results： MSC over-expressing HGF exhibited unchanged phenotype, proliferation and differentiation properties as compared with the control. However, in the mixed lymphocyte reaction, MSC-HGF could inhibit lymphocyte proliferation induced by heterogenic antigen in a dose-dependent manner. When the ratio of MSC to lymphocyte cells was 1 ： 80, the proliferation of lymphocytes decreased by 19. 8% in the MSC group and by 68.3% in the MSC-HGF group,which was 3.45 times that of the MSC group. Conclusion： Human bone marrow-derived MSCs modified by HGF gene maintain their inherent proliferative and differentiative ability, and show more potent immunosuppressive effect on in vitro cellular immune reaction, suggesting the novel clinical potentials of MSC in hepatopoietic stem cell transplantation or organ transplantation.

关 键 词：肝细胞生长因子 间充质干细胞 免疫抑制 基因转染 

分 类 号：R392[医药卫生—免疫学]