肿瘤坏死因子对间充质干细胞体内外免疫调节作用的影响  

Effects of Tumor Necrosis Factor-α on Immunoregulatory Activities of Mesenchymal Stem Cells in vitro and in vivo

作　　者：王勇奇[1,2,3] 李志勇[4] 曹小芳[2] 王恒湘[1] 郭子宽[2] 

机构地区：[1]空军总医院血液科,北京100142 [2]军事医学科学院放射与辐射医学研究所实验血液学研究室,北京100850 [3]安徽医科大学,安徽合肥230032 [4]新乡医学院,河南新乡453003

出　　处：《中国实验血液学杂志》2012年第4期981-984,共4页Journal of Experimental Hematology

基　　金：国家自然科学基金(编号30871018和30971068)

摘　　要：间充质干细胞(MSC)具有特征性的免疫调节作用;然而MSC对胶原诱导性关节炎(CIA)无治疗作用。肿瘤坏死因子-α(TNF-α)是类风湿性关节炎发生发展中的关键因素,因此本研究利用人脐带MSC为研究对象,观察TNF-α处理后MSC细胞内炎性反应相关转录因子NF-κB核转移情况;利用MTT法检测TNF-α对MSC增殖的影响;以SD大鼠脾脏为刺激细胞,Wistar大鼠脾脏单个核细胞为反应细胞,观察MSC对混合淋巴细胞反应的抑制作用;以Wistar大鼠CIA模型为研究对象,探讨MSC或TNF-α处理的MSC的治疗作用,用膝关节病理评分记录治疗效果。结果表明:TNF-α处理后NF-κB迅速从胞浆内转移至细胞核,但这种作用不影响MSC体外增殖。在不同细胞浓度条件下,无论用TNF-α处理与否,MSC均可显著抑制淋巴细胞增殖(均P<0.001);TNF-α处理的MSC有更强的抑制作用,在低细胞密度条件下尤为显著。然而,病理分析显示,MSC治疗组关节炎性浸润显著加重,病理评分明显高于未治疗组(P<0.05)。结论:TNF-α对体内外MSC的免疫调节作用具有不同的影响,其机制尚需进一步阐明。Mesenchymal stem cells （MSC） are characterized by their potent immuno-regulatory activity, however our previous data have shown that MSC have no therapeutic effects on collagen-induced arthritis （CIA）. To further clarify the complexity, the effects of tumor necrosis factor-alpha （TNF-α） on the in vitro and in vivo immunoregulatory activity of MSC were investigated in this study, as TNF-α is recognized as the key factor in the development of rheumatoid arthritis. The nuclear translocation of the inflammation-associated factor NF-κB was observed after human umbilical cord MSC were treated with TNF-α and the cell proliferation status was assessed by MTT test. The inhibitory effects of MSC or TNF-α-treated MSC on the mixed lymphocyte reaction, in which Wistar rat spleen mononuclear cells were served as the responders and the splenocytes from SD rat spleens as the stimulators, were also determined by the MTT test. Further, the therapeutic potentials of MSC or TNF-α-treated MSC were observed in a Wistar rat CIA model. The results showed that NF-κB translocated into the nuclei promptly after TNF-α treatment, though TNF-α had little effect on the MSC proliferation. MSC, whether pre-stimulated by TNF-α or not and when different doses were tested, exhibited obviously inhibitory effects on the proliferation of the lymphocytes （ P 〈 0. 001 for all groups tested）, while MSC-treated by TNF-α displayed more potent suppression especially when low-density were used. Unexpectedly, the infiltration of inflammatory ceils into the involved knees was aggravated by cell treatment and the pathological scores were significantly higher than those of controls （P 〈 0.05）. It is concluded that the TNF-α exhibits different effects on immune regulation activity of MSC, and its underlying mechanism needs to further investigate.

关 键 词：肿瘤坏死因子Α 间充质干细胞 胶原诱导关节炎 免疫调节 

分 类 号：R392.12[医药卫生—免疫学]