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去细胞化细胞外基质水凝胶:流变学特性及对人肾小球内皮细胞包封的反应。

Kidney decellularized extracellular matrix hydrogels: Rheological characterization and human glomerular endothelial cell response to encapsulation.

机构信息

Department of Biomedical Engineering, Northwestern University, Evanston, Illinois.

Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, Illinois.

出版信息

J Biomed Mater Res A. 2018 Sep;106(9):2448-2462. doi: 10.1002/jbm.a.36439.

Abstract

Hydrogels, highly-hydrated crosslinked polymer networks, closely mimic the microenvironment of native extracellular matrix (ECM) and thus present as ideal platforms for three-dimensional cell culture. Hydrogels derived from tissue- and organ-specific decellularized ECM (dECM) may retain bioactive signaling cues from the native tissue or organ that could in turn modulate cell-material interactions and response. In this study, we demonstrate that porcine kidney dECM can be processed to form hydrogels suitable for cell culture and encapsulation studies. Scanning electron micrographs of hydrogels demonstrated a fibrous ultrastructure with interconnected pores, and rheological analysis revealed rapid gelation times with shear moduli dependent upon the protein concentration of the hydrogels. Conditionally-immortalized human glomerular endothelial cells (GEnCs) cultured on top of or encapsulated within hydrogels exhibited high cell viability and proliferation over a one-week culture period. However, gene expression analysis of GEnCs encapsulated within kidney dECM hydrogels revealed significantly lower expression of several relevant genes of interest compared to those encapsulated within hydrogels composed of only purified collagen I. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A:2448-2462, 2018.

摘要

水凝胶是高度水合的交联聚合物网络,与天然细胞外基质(ECM)的微环境非常相似,因此是三维细胞培养的理想平台。源自组织和器官特异性脱细胞 ECM(dECM)的水凝胶可能保留来自天然组织或器官的生物活性信号,从而调节细胞-材料相互作用和反应。在这项研究中,我们证明了猪肾 dECM 可以加工成适合细胞培养和封装研究的水凝胶。水凝胶的扫描电子显微镜图显示出具有互连孔的纤维状超微结构,流变分析显示出快速的胶凝时间,剪切模量取决于水凝胶的蛋白质浓度。在水凝胶上培养或封装的条件永生化人肾小球内皮细胞(GEnC)在一周的培养期间表现出高细胞活力和增殖。然而,封装在肾 dECM 水凝胶中的 GEnC 的基因表达分析显示,与仅由纯化胶原 I 组成的水凝胶中封装的 GEnC 相比,几个相关感兴趣基因的表达明显降低。 © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A:2448-2462, 2018.

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