脐带间充质干细胞移植对系统性红斑狼疮免疫系统的影响  

Umbilical cord mesenehymal stem cells transplantation for the immune system following systemic lupus erythematosus

作　　者：肖玉翠[1] 王吉波[1] 董静[1] 高宏[2] 梁宏达[1] 王丽[2] 辛苗苗[1] 

机构地区：[1]青岛大学医学院附属医院风湿免疫科,山东省青岛市266003 [2]青岛大学医学院附属医院干细胞研究中心,山东省青岛市266003

出　　处：《中国组织工程研究与临床康复》2011年第19期3489-3493,共5页Journal of Clinical Rehabilitative Tissue Engineering Research

摘　　要：背景:目前有关脐带间充质干细胞对系统性红斑狼疮的免疫抑制作用及对各个脏器的影响报道较少。目的:探讨脐带间充质干细胞治疗MRL/lpr狼疮鼠的疗效及对免疫系统和各个脏器的影响。方法:MRL/lpr狼疮小鼠随机分为对照组、环磷酰胺组、环磷酰胺+脐带间充质干细胞组、脐带间充质干细胞组。对照组给以生理盐水,其他各组分别给予相应的治疗。采用考马斯亮蓝法检测24h尿蛋白定量;酶联免疫吸附法检测白细胞介素10、白细胞介素17、干扰素γ、PDGF、抗ds-DNA抗体;间接免疫荧光法检测抗核抗体水平;常规病理苏木精-伊红染色观察小鼠的肾脏病理改变肾脏病理改变;免疫组织化学法检测间充质干细胞表面标志CD44、CD105在肾脏、肺脏、脾脏中的表达。结果与结论:①环磷酰胺+脐带间充质干细胞组干扰素γ、白细胞介素17、白细胞介素10水平与对照组相比明显降低(P<0.05)。②32周时环磷酰胺+脐带间充质干细胞组和脐带间充质干细胞组尿蛋白定量低于环磷酰胺组和对照组(P<0.01)。③32周时环磷酰胺+脐带间充质干细胞组抗ds-DNA抗体水平与对照组相比明显降低。④脐带间充质干细胞组肾小球硬化及炎性细胞浸润程度均较对照组为轻。⑤32周时肾脏、肺脏、脾脏中间充质干细胞表面标志CD44、CD105表达为阴性。提示,应用脐带间充质干细胞移植治疗MRL/lpr狼疮鼠可以显著降低狼疮活动指标,对狼疮肾炎具有治疗作用,同时可以通过降低促炎因子的水平发挥免疫抑制作用。BACKGROUND： Recently,many studies indicate that umbilical cord mesenehymal stem cells （UC-MSCs） have therapeutic effects on systemic lupus erythematosus （SLE）.There are few reports,however,regarding the immunosuppressive effect and the organs of UC-MSCs on SLE .OBJECTIVE： To investigate the efficacy and influence of UC-MSCs transplantation on immune systems and different organs in the treatment of SLE.METHODS： MRL/lpr female mice were divided into 4 groups： control group,cyclophosphamide （CTX） group,CTX＋UC-MSCs group,and UC-MSCs group.24-hour proteinuria was assessed using Bradford method.Enzyme-linked immunosorbent assay was used to measure the levels of serum anti-dsDNA antibodies and interleukin-10 （IL-10）,IL-17,interferon gamma （IFN-γ）,PDGF.The histopathology changes of the kidney were observed using hematoxylin-eosin staining,and the UC-MSCs surface marks CD105 and CD44 in the kidney,lung and spleen were observed.RESULTS AND CONCLUSION： ①The levels of IL-10,IL-17 and IFN-γ in the CTX＋UC-MSCs group was lower than those in the control group （P 0.05）.②At 2 weeks,the 24-hour proteinuria in the CTX＋UC-MSCs and UC-MSCs groups was lower than that in the CTX and control groups （P 0.01）.③The serum level of anti ds-DNA antibodies in the CTX＋UC-MSCs group was significantly decreased as compared with that in the control group.④After UN-MSCs transplantation,glomerulosclerosis and inflammatory cells infiltrating degree relieved.⑤At 32 weeks,the expression of CD105 and CD44 in the kidney,lung and spleen was negative.The results indicated that MSCs transplantation can reduce lupus activity of MRL/lpr mice significantly and have marked therapeutic effect for lupus nephritis.It can also inhibit immune system by reducing the levels of inflammatory factors.

关 键 词：脐带 间充质干细胞 细胞移植 红斑狼疮 系统性 小鼠 近交MRL/lpr 

分 类 号：R394.2[医药卫生—医学遗传学]