Vajkoczy P, Menger M D, Simpson E, Messmer K
Institute for Surgical Research, University of Munich, Germany.
Transplantation. 1995 Jul 27;60(2):123-7.
Although the microvascular endothelium has been identified as the primary target site for the initiation of pancreatic islet graft rejection, little is known of the microvascular and cellular mechanisms involved, partly due to the lack of adequate models. Herein, we present a model for the in vivo assessment of the microcirculation of pancreatic islet grafts in mice. Isolated islets of Langerhans from immunocompetent hairless mice and immunoincompetent athymic nude mice were transplanted syngeneically into a specially designed dorsal skinfold chamber mounted on nondiabetic recipients. The islets' microcirculation was visualized by means of intravital fluorescence microscopy, and microcirculatory parameters were quantitatively analysed over a period of 14 days in the awake animal. Between day 2 and 4 after transplantation 84% (31/37; hairless mice) and 69% (36/52; nude mice) of the islet grafts revealed capillary sprouts and formation of new microvessels. On day 6, these sprouts were found interconnected, and red blood cell movement within the newly formed microvascular network was observed. The process of angiogenesis and revascularization was completed within 10 days after transplantation yielding a glomerulus-like network of capillaries as known for pancreatic islets in situ. Functional capillary density of the islet grafts ranged between 650 and 700 cm-1 in both hairless and nude mice. Within the islets' microvessels neither accumulation of leukocytes nor leukocyte-endothelial cell interaction was observed, indicating the lack of rejection and inflammation in these syngeneic islet grafts. We propose that this model provides a wide spectrum of promising experimental approaches for the study of microcirculatory and cellular mechanisms in free pancreatic islet transplantation.
尽管微血管内皮已被确定为胰岛移植排斥反应起始的主要靶位点，但对于其中涉及的微血管和细胞机制却知之甚少，部分原因是缺乏合适的模型。在此，我们展示一种用于体内评估小鼠胰岛移植微循环的模型。将来自具有免疫活性的无毛小鼠和免疫缺陷的无胸腺裸鼠的分离胰岛同基因移植到安装在非糖尿病受体身上的特制背部皮褶小室中。通过活体荧光显微镜观察胰岛的微循环，并在清醒动物中对微循环参数进行了为期14天的定量分析。移植后第2天至第4天，84%（31/37；无毛小鼠）和69%（36/52；裸鼠）的胰岛移植体出现毛细血管芽和新微血管的形成。在第6天，发现这些芽相互连接，并观察到新形成的微血管网络内有红细胞流动。血管生成和再血管化过程在移植后10天内完成，形成了胰岛原位所见的类似肾小球的毛细血管网络。无毛小鼠和裸鼠的胰岛移植体的功能性毛细血管密度在650至700 cm-1之间。在胰岛微血管内未观察到白细胞的聚集或白细胞与内皮细胞的相互作用，表明这些同基因胰岛移植体不存在排斥和炎症反应。我们认为该模型为研究游离胰岛移植中的微循环和细胞机制提供了一系列有前景的实验方法。
