Layer-by-layer cell coating technique using extracellular matrix facilitates rapid fabrication and function of pancreatic β-cell spheroids
Layer-by-layer cell coating technique using extracellular matrix facilitates rapid fabrication and function of pancreatic β-cell spheroids
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DOI：
10.1016/j.biomaterials.2018.01.020
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发表时间：
2018-04-01
期刊：
影响因子：
14
通讯作者：
Akashi, Mitsuru
中科院分区：
文献类型：
--
作者：
Fukuda, Yasunari;Akagi, Takami;Akashi, Mitsuru
可用材料和制造技术的发展推动了利用替代胰岛移植的胰岛素分泌细胞的组织工程。我们已经建立了一种细胞包被技术，使细胞表面被细胞外基质的基础上的一层一层（LbL）组件的概念。本研究评估了该技术是否有利于使用小鼠β细胞系制造胰腺β细胞球体。LbL包被的细胞可以立即构建结构良好、致密的球状体。在功能分析中，具有LbL包被细胞的球状体与具有非包被细胞的球状体相比具有更大的胰岛素分泌能力，胰岛素和葡萄糖转运蛋白2基因的表达增加。此外，我们发现，连接蛋白36，间隙连接分子的表达上调LbL细胞涂层。当与LbL包被的细胞的球体同基因移植在糖尿病小鼠，血糖水平立即降低和葡萄糖敏感性显着改善腹膜内葡萄糖刺激后相比，非包被的细胞的球体。这种细胞包被技术将是一种临床上适用的方法，用于制造胰腺β细胞球体和治疗1型糖尿病。(C)2018爱思唯尔有限公司版权所有
Tissue engineering of insulin-secreting cells using alternatives to islet transplantation has been fueled by the development of available materials and fabrication techniques. We have established a cell coating technique that enables the cell surface to be coated with extracellular matrix based on the concept of a layer-by-layer (LbL) assembly. The present study evaluated whether this technique is beneficial for fabricating pancreatic beta-cell spheroids using a mouse beta-cell line. The well-structured and dense spheroids could immediately be constructed by the LbL-coated cells. In the functional analysis, spheroids with the LbL-coated cells had greater insulin secretion ability with increased expression of the insulin and glucose transporter 2 genes versus spheroids with non-coated cells. In addition, we found that the expression of connexin 36, a gap junction molecule, was upregulated by the LbL cell coating. When spheroids with the LbL-coated cells were syngeneically transplanted in diabetic mice, blood glucose levels immediately decreased and glucose sensitivity significantly improved after intraperitoneal glucose stimulation compared to spheroids with non-coated cells. This cell coating technique would be a clinically applicable approach for fabricating pancreatic beta-cell spheroids and treating type 1 diabetes mellitus. (C) 2018 Elsevier Ltd. All rights reserved.