An cell-assembly derived physiological 3D model of the metabolic syndrome, based on adipose-derived stromal cells and a gelatin/alginate/fibrinogen matrix
An cell-assembly derived physiological 3D model of the metabolic syndrome, based on adipose-derived stromal cells and a gelatin/alginate/fibrinogen matrix
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基于脂肪基质细胞和明胶/藻酸盐/纤维蛋白原基质的细胞组装衍生的代谢综合征生理 3D 模型
DOI：
10.1016/j.biomaterials.2010.01.111
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发表时间：
2010-05-01
期刊：
影响因子：
14
通讯作者：
Ge, Yakun
中科院分区：
文献类型：
--
作者：
Xu, Mingen;Wang, Xiaohong;Ge, Yakun
药物发现的主要障碍之一是缺乏能够捕捉疾病更复杂特征的体外三维（3D）模型。本研究利用细胞组装技术（cell-assembly technology， CAT）建立代谢综合征（MS）体外生理模型，将细胞组装到指定位置形成复杂的三维结构。用明胶/海藻酸盐/纤维蛋白原组装脂肪源基质（ADS）细胞。纤维蛋白作为调控ADS细胞分化和自组织的有效物质。ADS细胞分化为脂肪细胞和内皮细胞，同时诱导细胞自组织形成类似的组织结构。胰岛在指定位置沉积，与脂肪细胞构成脂肪轴。通过对能量代谢相关因素的分析发现，该系统可以捕捉更多MS的病理特征，已知对MS有作用的药物在该系统中表现出一致的作用，表明该模型在MS药物发现中具有潜力。总之，本研究表明，结合CAT技术可以调节细胞的分化和自组织。该模型有助于更好地理解多发性硬化症的发病机制，并有助于开发新的药物发现技术。(C) 2010 Elsevier Ltd.版权所有。
One of the major obstacles in drug discovery is the lack of in vitro three-dimensional (3D) models that can capture more complex features of a disease. Here we established a in vitro physiological model of the metabolic syndrome (MS) using cell-assembly technique (CAT), which can assemble cells into designated places to form complex 3D structures. Adipose-derived stromal (ADS) cells were assembled with gelatin/alginate/fibrinogen. Fibrin was employed as an effective material to regulate ADS cell differentiation and self-organization along with other methods. ADS cells differentiated into adipocytes and endothelial cells, meanwhile, the cells were induced to self-organize into an analogous tissue structure. Pancreatic islets were then deposited at designated locations and constituted the adipoinsular axis with adipocytes. Analysis of the factors involved in energy metabolism showed that this system could capture more pathological features of MS. Drugs known to have effects on MS showed accordant effects in this system, indicating that the model has potential in MS drug discovery. Overall, this study demonstrated that cell differentiation and self-organization can be regulated by techniques combined with CAT. The model presented could result in a better understanding of the pathogenesis of MS and the development of new technologies for drug discovery. (C) 2010 Elsevier Ltd. All rights reserved.