Pancreatic duct cells in human islet cell preparations are a source of angiogenic cytokines interleukin-8 and vascular endothelial growth factor.
Pancreatic duct cells in human islet cell preparations are a source of angiogenic cytokines interleukin-8 and vascular endothelial growth factor.
复制标题
DOI：
10.2337/db07-1705
复制
发表时间：
2008-08
期刊：
影响因子：
7.7
通讯作者：
Pipeleers D
中科院分区：
文献类型：
--
作者：
Movahedi B;Gysemans C;Jacobs-Tulleneers-Thevissen D;Mathieu C;Pipeleers D
人类胰岛细胞植入物的植入和功能被认为依赖于其快速和充分的血管重建。对啮齿类动物胰岛移植物的研究表明，β细胞表达血管内皮生长因子（VEGF）可促进这一过程。目前的工作检查是否人胰岛制剂产生VEGF以及白细胞介素（IL）-8，另一种血管生成蛋白，并评估污染导管细胞在VEGF和IL-8介导的血管生成的作用。研究设计和方法-比较人胰岛和胰管细胞制备物在培养期间以及移植到非肥胖糖尿病（NOD）/scid小鼠后各自的VEGF和IL-8表达和产生。在体外主动脉环测定和体内鸡胚绒毛尿囊膜测定中测量相关的血管生成作用。与培养的人胰岛内分泌细胞相比，培养的胰管细胞表达的VEGF和IL-8分别高3倍和10倍，并在血管生成水平释放这两种蛋白质。纯化的导管细胞的血管生成作用高于纯化的内分泌胰岛细胞，并且被IL-8和VEGF抗体的组合完全阻断。在NOD/scid小鼠肾包膜下的人导管细胞植入物表达比人胰岛细胞植入物更高水平的IL-8和VEGF，并在移植后第一天诱导循环IL-8和VEGF水平。结论：人导管细胞释放的IL-8和VEGF可能有助于目前使用的人胰岛细胞移植物的血管再生。进一步的工作应该检查这种效应是否以及何时可以胜过这种细胞类型的其他炎症和免疫影响。
OBJECTIVE—Engraftment and function of human islet cell implants is considered to be dependent on their rapid and adequate revascularization. Studies with rodent islet grafts have shown that vascular endothelial growth factor (VEGF) expression by β-cells can promote this process. The present work examines whether human islet preparations produce VEGF as well as interleukin (IL)-8, another angiogenic protein, and assesses the role of contaminating duct cells in VEGF and IL-8–mediated angiogenesis. RESEARCH DESIGN AND METHODS—Human islet and pancreatic duct cell preparations are compared for their respective expression and production of VEGF and IL-8 during culture as well as following transplantation in nonobese diabetic (NOD)/scid mice. The associated angiogenic effects are measured in an in vitro aortic ring assay and in an in vivo chick embryo chorioallantoic membrane assay. RESULTS—Cultured pancreatic duct cells expressed 3- and 10-fold more VEGF and IL-8, respectively, than cultured human islet endocrine cells and released both proteins at angiogenic levels. The angiogenic effect of purified duct cells was higher than that of purified endocrine islet cells and was completely blocked by a combination of IL-8 and VEGF antibodies. Human duct cell implants under the kidney capsule of NOD/scid mice expressed higher levels of IL-8 and VEGF than human islet cell implants and induced circulating IL-8 and VEGF levels during the first day posttransplantation. CONCLUSIONS—Human duct cell–released IL-8 and VEGF may help revascularization of currently used human islet cell grafts. Further work should examine whether and when this effect can prevail over other inflammatory and immune influences of this cell type.
登录
查看更多内容
影响因子：
7.7
作者：
Davalli, AM;Scaglia, L;Weir, GC
通讯作者：
Weir, GC
影响因子：
1.3
作者：
ANDERSON, SP;DEPALMA, A;THISSE, JF
通讯作者：
THISSE, JF
影响因子：
5.8
作者：
Pavlovic, D;VandeWinkel, M;Pipeleers, D
通讯作者：
Pipeleers, D
DOI：
10.1084/jem.167.6.1883
发表时间：
1988-06-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Matsushima K;Morishita K;Yoshimura T;Lavu S;Kobayashi Y;Lew W;Appella E;Kung HF;Leonard EJ;Oppenheim JJ
通讯作者：
Oppenheim JJ
影响因子：
6.2
作者：
Lai, Y;Schneider, D;Linn, T
通讯作者：
Linn, T