不同移植途径对人脐带间充质干细胞防治NOD鼠糖尿病的影响  

Effects of different transplantation pathways of hUCMSCs on prevention of type 1 diabetes in NOD mice

作　　者：李青[1] 谢洪彬[1] 王云帅[1] 齐晖[1] 李富荣[1] 

机构地区：[1]暨南大学第二临床医学院深圳市人民医院医学研究中心,518020

出　　处：《免疫学杂志》2012年第5期398-402,共5页Immunological Journal

基　　金：国家自然科学基金(30772042);广东省自然科学基金(6027540)

摘　　要：目的观察不同移植途径对人脐带间充质干细胞(hUCMSCs)预防非肥胖型糖尿病(NOD)小鼠糖尿病发病的影响并进一步探索其机制。方法通过胰腺包膜下和尾静脉向4周龄雌性NOD小鼠注射hUCMSCs-EGFP/luc,活体成像观察hUCMSCs的分布。动态监测NOD小鼠血糖水平变化以及Treg/Th17细胞变化,在30周龄时处死小鼠进行胰腺炎评级。结果胰腺移植组在30周龄时糖尿病发病率显著低于尾静脉移植组和对照组。2种途径移植组小鼠Treg细胞呈升高趋势,明显高于对照组,而Th17细胞明显低于对照组,2种移植途径组间无明显差异。病理学发现胰腺组胰腺炎评分最低,对照组最高,移植组胰腺炎性损伤明显减轻。结论 hUCMSCs经2种途径移植后,均能明显降低NOD鼠糖尿病的发生率和延缓发病时间,且胰腺移植组效果显著。除hUCMSCs主要通过诱导Treg细胞抑制Th17细胞发挥免疫抑制作用,阻止自身免疫对胰岛β细胞的攻击外,可能与到达胰腺组织的细胞对胰腺β细胞的保护和损伤修复作用也具有一定关系。The aim of this study was to study the effects of different transplantation pathways of hUCMSCs on prevention type 1 diabetes in NOD mice and the immunologic intervention mechanism.hUCMSCs-EGFP/luc were injected into the pancreas or tail vein of NOD mice aged 4 weeks.Distribution of hUCMSCs in vivo was monitored by bioluminescence imaging.Blood glucose levels,the frequency of Treg and Th17 cells in spleen of NOD mice were monitored by flow cytometry.At the age of 30 weeks,pancreatic histopathologic studies were performed for insulitis score by hematoxylin eosin staining.Bioluminescence images showed that the hUCMSCs transplanted into the pancreatic capsule were survived in pancreas only,while hUCMSCs in tail vein-injected mice was mainly localized in the lung and disappeared after 5 days.The incidence of diabetes in pancreatic transplantation group was obviously lower than that in tail-injected group and control group.In the two transplantation groups,the frequency of Treg was increased but the frequency of Th17 decreased as compared to control group.But there was no difference between the two transplantation groups.Furthermore,insulitis score in pancreatic group was the lowest in the three groups.The above result indicated that hUCMSCs transplanted via the two different pathways can reduce the incidence of diabetes in NOD mice.And the pancreas group demonstrates the best effect.hUCMSCs may prevent autoimmune attack on islet β cell by inducing Treg cells,inhibiting Th17 cells.Additionally,the mechanism maybe related to the protection and repair effects of hUCMSCs on islet β cells in pancreas.

关 键 词：人脐带间充质干细胞 1型糖尿病 TREG细胞 TH17细胞 

分 类 号：R587.1[医药卫生—内分泌]