Jain Neha, Lee Eun Jung
New Jersey Institute of Technology, Department of Biomedical Engineering, Newark, NJ, USA.
Cell Transplant. 2016;25(1):97-108. doi: 10.3727/096368915X687732. Epub 2015 Mar 6.
The islet endothelium comprises a specialized population of islet endothelial cells (IECs) expressing unique markers such as nephrin and α-1 antitrypsin (AAT) that are not found in endothelial cells in surrounding tissues. However, due to difficulties in isolating and maintaining a pure population of these cells, the information on these islet-specific cells is currently very limited. Interestingly, we have identified a large subpopulation of endothelial cells exhibiting IEC phenotype, while deriving insulin-producing cells from mouse embryonic stem cells (mESCs). These cells were identified by the uptake of low-density lipoprotein (LDL) and were successfully isolated and subsequently expanded in endothelial cell culture medium. Further analysis demonstrated that the mouse embryonic stem cell-derived endothelial cells (mESC-ECs) not only express classical endothelial markers, such as platelet endothelial cell adhesion molecule (PECAM1), thrombomodulin, intercellular adhesion molecule-1 (ICAM-1), and endothelial nitric oxide synthase (eNOS) but also IEC-specific markers such as nephrin and AAT. Moreover, mESC-ECs secrete basement membrane proteins such as collagen type IV, laminin, and fibronectin in culture and form tubular networks on a layer of Matrigel, demonstrating angiogenic activity. Further, mESC-ECs not only express eNOS, but also its eNOS expression is glucose dependent, which is another characteristic phenotype of IECs. With the ability to obtain highly purified IECs derived from pluripotent stem cells, it is possible to closely examine the function of these cells and their interaction with pancreatic β-cells during development and maturation in vitro. Further characterization of tissue-specific endothelial cell properties may enhance our ability to formulate new therapeutic angiogenic approaches for diabetes.
胰岛内皮由一群特殊的胰岛内皮细胞（IECs）组成，这些细胞表达独特的标志物，如nephrin和α-1抗胰蛋白酶（AAT），而周围组织的内皮细胞中未发现这些标志物。然而，由于分离和维持这些细胞的纯群体存在困难，目前关于这些胰岛特异性细胞的信息非常有限。有趣的是，在从小鼠胚胎干细胞（mESCs）中诱导产生胰岛素生成细胞的过程中，我们鉴定出了一大群表现出IEC表型的内皮细胞。这些细胞通过摄取低密度脂蛋白（LDL）得以鉴定，并成功分离出来，随后在内皮细胞培养基中进行扩增。进一步分析表明，小鼠胚胎干细胞衍生的内皮细胞（mESC-ECs）不仅表达经典的内皮标志物，如血小板内皮细胞黏附分子（PECAM1）、血栓调节蛋白、细胞间黏附分子-1（ICAM-1）和内皮型一氧化氮合酶（eNOS），还表达IEC特异性标志物，如nephrin和AAT。此外，mESC-ECs在培养过程中分泌基底膜蛋白，如IV型胶原、层粘连蛋白和纤连蛋白，并在基质胶层上形成管状网络，显示出血管生成活性。此外，mESC-ECs不仅表达eNOS，而且其eNOS表达还依赖于葡萄糖，这是IECs的另一个特征性表型。由于能够从多能干细胞中获得高度纯化的IECs，因此有可能在体外密切研究这些细胞在发育和成熟过程中的功能以及它们与胰腺β细胞的相互作用。对组织特异性内皮细胞特性的进一步表征可能会增强我们制定针对糖尿病的新治疗性血管生成方法的能力。
