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健康和糖尿病内皮细胞在形貌线索上的功能差异。

Functional differences between healthy and diabetic endothelial cells on topographical cues.

机构信息

Mechanobiology Institute, National University of Singapore, T-Lab, #10-01, 5A Engineering Drive 1, Singapore, 117411; Department of Biomedical Engineering, Block E4 #04-08, 4 Engineering Drive 3, National University of Singapore, 117583, Singapore.

Department of Biomedical Engineering, Block E4 #04-08, 4 Engineering Drive 3, National University of Singapore, 117583, Singapore.

出版信息

Biomaterials. 2018 Jan;153:70-84. doi: 10.1016/j.biomaterials.2017.10.037. Epub 2017 Oct 25.

Abstract

The endothelial lining of blood vessels is severely affected in type II diabetes. Yet, there is still a paucity on the use of diabetic endothelial cells for study and assessment of implantable devices targeting vascular disease. This critically impairs our ability to determine appropriate topographical cues to be included in implantable devices that can be used to maintain or improve endothelial cell function in vivo. Here, the functional responses of healthy and diabetic human coronary arterial endothelial cells were studied and observed to differ depending on topography. Gratings (2 μm) maintained normal endothelial functions such as adhesiveness, angiogenic capacity and cell-cell junction formation, and reduced immunogenicity of healthy cells. However, a significant and consistent effect was not observed in diabetic cells. Instead, diabetic endothelial cells cultured on the perpendicularly aligned multi-scale hierarchical gratings (250 nm gratings on 2 μm gratings) drastically reduced the uptake of oxidized low-density lipoprotein, decreased immune activation, and accelerated cell migration. Concave microlens (1.8 μm diameter) topography was additionally observed to overwhelmingly deteriorate diabetic endothelial cell function. The results of this study support a new paradigm and approach in the design and testing of implantable devices and biomedical interventions for diabetic patients.

摘要

血管内皮细胞在 2 型糖尿病中受到严重影响。然而,对于使用糖尿病内皮细胞来研究和评估针对血管疾病的植入式设备,我们的了解仍然很少。这极大地限制了我们确定适当的地形线索的能力,这些线索可以包含在植入式设备中,以维持或改善体内的内皮细胞功能。在这里,研究了健康和糖尿病人类冠状动脉内皮细胞的功能反应,并观察到它们的功能反应因地形而异。格栅(2 μm)保持了健康细胞的正常内皮功能,如黏附性、血管生成能力和细胞-细胞连接形成,并降低了健康细胞的免疫原性。然而,在糖尿病细胞中并没有观察到明显一致的效果。相反,在垂直排列的多尺度分级格栅(2 μm 格栅上的 250 nm 格栅)上培养的糖尿病内皮细胞大大降低了氧化型低密度脂蛋白的摄取,减少了免疫激活,并加速了细胞迁移。此外,还观察到凹微透镜(1.8 μm 直径)地形严重恶化了糖尿病内皮细胞的功能。这项研究的结果支持了一种新的范例和方法,用于设计和测试植入式设备和针对糖尿病患者的生物医学干预措施。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a938/5724387/443763d9afe3/nihms919663f1.jpg

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