Adipose mesenchymal stem cells promote the function and survival of islet graft during co-transplantation

Z. Jiao, W. Xue, Maozhu An, Q. Fan, Yang Li, Fenglou Li, Zuohua Zhang
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Abstract

Objective To explore the function and survival of islet grafts during co-transplantation with adipose mesenchymal stem cells (AMSCs) in diabetic mice. Methods After human AMSCs and islet cells were isolated, purified and then subcutaneously co-transplanted into nude mice with diabetes mellitus. Four groups of AMSCs + islet co-transplantation, islet transplantation alone, phosphate buffered solution (PBS) and normal control mice were designated. Islet cell activity and apoptosis/revascularization degree of islet grafts were observed by immunohistochemical double staining of insulin, factor associated suicide (Fas) and CD31 antibody. The blood glucose and serum insulin levels of mice and the survival time of islet grafts were compared. Results The blood glucose and serum insulin levels of diabetic mice analyzed by multivariate analysis in AMSCs + islet co-transplantation group were better than those in islet transplantation alone group (P<0.05). The mean survival time (MST) of islet grafts was longer in AMSCs + islet co-transplantation group than that in islet transplantation alone group [(81.33±7.58) vs. (58.17±6.91) days] (P<0.05). At Day 7 post-transplantation, insulin staining intensity of islet grafts was higher in AMSCs + islet co-transplantation group than that in islet transplantation alone group while Fas staining intensity of islet grafts was lower. And mean microvascular density (MVD) of islet grafts per square millimeter was higher in AMSCs + islet co-transplantation group than that in islet transplantation alone group [(21.8±5.6) vs. (14.6±4.1)] (P<0.05). Conclusions Co-transplantation with AMSCs may improve the function of islet grafts, prolong its survival and promote its revascularization. Key words: Islet of Langerhans transplantation; Adipose mesenchymal stem cells; Diabetes mellitus
脂肪间充质干细胞在共移植过程中促进胰岛移植物的功能和存活
目的探讨胰岛移植物与脂肪间充质干细胞(AMSCs)共移植对糖尿病小鼠的功能和存活率的影响。方法分离纯化人造血干细胞和胰岛细胞后,皮下共移植到糖尿病裸鼠体内。将AMSCs +胰岛共移植、胰岛单独移植、磷酸盐缓冲液(PBS)和正常对照小鼠分为4组。采用胰岛素、自杀相关因子(factor associated suicide, Fas)和CD31抗体免疫组化双染法观察胰岛移植后胰岛细胞活性和凋亡/血运重建程度。比较小鼠的血糖和血清胰岛素水平及胰岛移植的存活时间。结果多因素分析显示,AMSCs +胰岛共移植组糖尿病小鼠血糖和血清胰岛素水平明显高于单独胰岛移植组(P<0.05)。AMSCs +胰岛共移植组胰岛移植的平均生存时间(MST)长于单独胰岛移植组[(81.33±7.58)∶(58.17±6.91)d] (P<0.05)。移植后第7天,AMSCs +胰岛共移植组胰岛移植物胰岛素染色强度高于单独胰岛移植组,而胰岛移植物Fas染色强度低于单独胰岛移植组。AMSCs +胰岛共移植组胰岛移植物每平方毫米的平均微血管密度(MVD)高于单独胰岛移植组[(21.8±5.6)比(14.6±4.1)](P<0.05)。结论与AMSCs共移植可改善胰岛移植物的功能,延长其存活时间,促进其血运重建。关键词:朗格汉斯胰岛移植;脂肪间充质干细胞;糖尿病
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