中山大学学报(医学科学版)2012,Vol.33Issue(2):168-171,183,5.
CD40LIg基因修饰骨髓间充质干细胞对异种胰岛移植排斥反应的抑制作用
Effects of CD40LIg Modified Bone Marrow Mesenchymal Stem Cells on Rejection of Rat Islet Xenografts
摘要
Abstract
[Objective] To investigate the effects of cluster of differentiation 40 ligand immunoglobulin (CD40Iig) modified bone marrow mesenchymal stem cells (MSC) on the rejection of rat islet xenografts. [Methods] The islet xenografts model was established with islet cells of Wistar rat transplant under the left kidney capsule of diabetic SD rat. MSC were infected with the recombinant adenoviruses containing CD40LIg gene as intervention treatment. Forty-five modeled diabetic rats were randomly divided into three groups with 15 in each; only islet cells were transplanted to rats in control group (A), islet cells and MSC were transplanted to rats in MSC group (B) and islet cells and MSC infected with CD40LJg gene were transplanted to rats in transfected MSC group (C). The blood sugar and the survival of transplantation rats and grafts were observed after transplantation. The morphological changes of grafts were observed. Expression of CD40LJg and insulin were detected by immunohistochemical staining and cytokines were quantified by ELISA. [Results] (1) The blood sugar of transplantation rats decreased to normal level on day 2 after transplantation. The average level blood glucose of control group (A), MSC group (B ), transfected MSC group (C) increased on day 7,20,47, after transplantation respectively. (2) The grafts of group A, B, and C survived for (9.5 ± 3.2), (25.2 ± 5.3), and(53.6 ± 7.5) days, respectively. There are significant deviation of the grafts survival among group A, B and C(F=6.821 ,P<0.05). The survival of transplantation rats were (24.1 ± 6.8), (51.7 ± 7.9),and(95.2 ± 12.7) days in group A, B, and C, respectively. The survival of transplantation rats compared each other were same as the survival of grafts (F=6.821,P< 0.05).(3)In group A, Serum IL-2 and TNF-α concentrationwere elevated to a high level within seven days post-transplantation and significantly increased compared with that pre-transplantation (P<0.01). Serum IL-4 and IL-10 concentration were significantly decreased compared with that pre-transplantation (P<0.01).(4) Hematoxylin-eosin staining of grafts showed islets bolus under the kidney capsule of transplantation rats, no inflammatory cell infiltrate and expression of insulin protein at islets in group B and C. The grafts positively stained for CD40LIg in group C. [Conclusion] CD40Llg gene modified bone marrow mesenchymal stem cells could prolong the survival time of islet xenografts and inhibit the rejection of islet xenografts.关键词
骨髓间充质干细胞/CD40LIg/胰岛移植/糖尿病Key words
islet xenografts/ diabetes mellitus/ bone marrow mesenchymal stem cells/ CD40LIg分类
医药卫生引用本文复制引用
张剑,张琪,张英才,朱焕兵,汪国营,杨扬..CD40LIg基因修饰骨髓间充质干细胞对异种胰岛移植排斥反应的抑制作用[J].中山大学学报(医学科学版),2012,33(2):168-171,183,5.基金项目
国家自然科学基金(81070382) (81070382)
广东省科技计划项目(2008B030301050) (2008B030301050)