移植途径对人脐带间充质干细胞治疗小鼠糖尿病效果的影响  

Transplantation of human umbilical cord mesenchymal stem cells through different approaches for treatment of diabetic mice

作　　者：蒋豆蔻 李青[1] 杨晓菲[1,2] 李阳[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,干细胞与细胞治疗重点实验室,广东深圳518020 [2]暨南大学医学院病理生理学系,广东广州510632

出　　处：《中国病理生理杂志》2017年第4期612-619,共8页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.81270857;No.81670702);广东省自然科学基金资助项目(No.2015A030313762);深圳市科技计划(No.JCYJ2016031115823245;No.CXZZ20140903103747568;No.JCYJ20140416122811921);博士后科学基金资助项目(No.2016M592603)

摘　　要：目的:观察不同途径移植人脐带间充质干细胞(hUCMSCs)对小鼠糖尿病的治疗效果。方法:利用增强绿色荧光蛋白和萤光素酶报告系统(EGFP/Luc)标记hUCMSCs,通过胰腺包膜下途径或尾静脉途径将携带萤光标记的hUCMSCs移植到链脲霉素诱导的糖尿病模型小鼠体内。移植后利用萤光素酶报告基因追踪hUCMSCs在活体内的迁移和定位;组织学检测小鼠胰岛形态变化;功能学实验动态检测小鼠血糖、血清胰岛素水平和糖耐量。结果:活体生物发光成像显示胰腺包膜下途径移植的hUCMSCs主要定位于胰腺,尾静脉途径移植的hUCMSCs主要定位于肺,仅少量细胞向胰腺部位迁移。组织学检测发现,胰腺包膜下途径移植的小鼠胰岛边界清晰,无炎症细胞浸润;而尾静脉途径移植的小鼠胰腺组织有少量炎症细胞浸润和纤维化形成。功能学检测发现胰腺包膜下移植较尾静脉移植降低小鼠血糖作用显著,血糖可降至接近正常水平,且血清胰岛素水平明显升高,葡萄糖的调节能力显著增强。结论:移植途径对hUCMSCs治疗糖尿病的效果有影响。胰腺包膜下移植在降低小鼠血糖、升高胰岛素水平及改善胰岛功能方面均优于尾静脉移植。AIM： To compare the therapeutic effects of transplantation of human umbilical cord mesenchymal stem cells（ h UCMSC） through different ways on diabetic mice. METHODS： hUCMSCs were labeled with enhanced green fluorescent protein（ EGFP） and luciferase（ Luc） reporter gene,and then the cells were transplanted into the diabetic mice through pancreas or tail vein to monitor the migration of the hUCMSCs in vivo. The pathological changes of pancreas tissue sections were determined by HE staining. Weight and blood glucose of the mice were measured dynamically. To compare the therapeutic effects,serum insulin levels were analyzed and glucose tolerance test were also performed. RESULTS： In vivo bioluminescence imaging results showed that the hUCMSCs transplanted into pancreatic capsule was mainly located in the pancreas while the hUCMSCs transplanted through vein tail injection was mainly located in the lung. HE staining illustrated that islet cells presented distinctive boundary and no infiltration of inflammatory cells in pancreatic capsule transplantation group was observed,but a little inflammatory cell infiltration and fibrosis formation in tail vein injection group were seen. A significant decrease in blood glucose level and a significant increase in serum insulin level in pancreas transplantation group were showed as compared with vein tail injection group. CONCLUSION： Transplantation of hUCMSCs through different approaches demonstrates different effects. The transplantation of hUCMSCs into pancreatic capsule is more effective on hyperglycemia reversion,insulin secretion and improvement of beta-cell function than that through tail vein.

关 键 词：人脐带间充质干细胞 移植 1型糖尿病 

分 类 号：R587.1[医药卫生—内分泌] R363[医药卫生—内科学]