Vessel Network Architecture of Adult Human Islets Promotes Distinct Cell-Cell Interactions In Situ and Is Altered After Transplantation
Vessel Network Architecture of Adult Human Islets Promotes Distinct Cell-Cell Interactions In Situ and Is Altered After Transplantation
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DOI：
10.1210/en.2016-1184
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发表时间：
2017-05-01
期刊：
影响因子：
4.8
通讯作者：
Speier, Stephan
中科院分区：
文献类型：
--
作者：
Cohrs, Christian M.;Chen, Chunguang;Speier, Stephan
胰岛细胞激素的释放受胰岛内内皮细胞和内分泌细胞信号的调节。然而，胰岛内血管化和旁分泌细胞信号传导的模型大多基于啮齿动物胰腺。我们评估了未受干扰的人胰岛原位血管网络的结构和内分泌细胞相互作用及其在体内移植后重建内源性血管网络的潜力。我们准备了从接受部分胰腺切除术的非糖尿病患者中获得的新鲜胰腺组织切片。此外，我们将人类供体胰岛移植到小鼠眼前房中。接下来，我们对胰岛细胞和血管结构进行了细胞分辨率的三维原位和体内成像，并将我们的研究结果与小鼠和猪胰岛进行了比较。我们的数据显示，与小鼠胰岛相比，人类的血管结构显著不同，血管直径减小，血管分支减少，总血管网络缩短。与人胰岛中独特的细胞排列一起，这限制了β与内皮细胞的相互作用，促进了a和B细胞的连接，并促进了胰岛内独立b细胞簇的形成。此外，我们的研究结果表明，在供体年龄相关的机制移植后，胰岛的内源性血管网络显着改变。因此，我们的研究提供了深入了解血管结构和细胞排列的人类胰岛细胞间胰岛信号传导的明显后果。此外，我们的研究结果表明，移植后的人胰岛植入可以通过使用替代的，不太成熟的胰岛细胞来源来改善。
Islet-cell hormone release is modulated by signals from endothelial and endocrine cells within the islet. However, models of intraislet vascularization and paracrine cell signaling are mostly based on the rodent pancreas. We assessed the architecture and endocrine cell interaction of the vascular network in unperturbed human islets in situ and their potential to re-establish their endogenous vascular network after transplantation in vivo. We prepared slices of fresh pancreas tissue obtained from nondiabetic patients undergoing partial pancreatectomy. In addition, we transplanted human donor islets into the anterior chamber of the mouse eye. Next, we performed three-dimensional in situ and in vivo imaging of islet cell and vessel architecture at cellular resolution and compared our findings with mouse and porcine islets. Our data reveal a significantly different vascular architecture with decreased vessel diameter, reduced vessel branching, and shortened total vessel network in human compared with mouse islets. Together with the distinct cellular arrangement in human islets, this limits beta to endothelial cell interactions, facilitates connection of a and b cells, and promotes the formation of independent b-cell clusters within islets. Furthermore, our results show that the endogenous vascular network of islets is significantly altered after transplantation in a donor age-related mechanism. Thus, our study provides insight into the vascular architecture and cellular arrangement of human islets with apparent consequences for intercellular islet signaling. Moreover, our findings suggest that human islet engraftment after transplantation can be improved by using alternative, less mature islet-cell sources.