The influence of elastin-like recombinant polymer on the self-renewing potential of a 3D tissue equivalent derived from human lamina propria fibroblasts and oral epithelial cells
The influence of elastin-like recombinant polymer on the self-renewing potential of a 3D tissue equivalent derived from human lamina propria fibroblasts and oral epithelial cells
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DOI：
10.1016/j.biomaterials.2011.04.054
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发表时间：
2011-09-01
期刊：
影响因子：
14
通讯作者：
Hasirci, Vasif
中科院分区：
文献类型：
--
作者：
Kinikoglu, Beste;Carlos Rodriguez-Cabello, Jose;Hasirci, Vasif
三维上皮组织等同物倾向于在培养过程中逐渐失去其自我更新潜力，因为其上皮细胞随着时间失去其增殖能力。尽管组织工程构建体可以很好地模拟天然组织，但由于等同物中增殖细胞的数量不足，其在植入后迅速降解。在本研究中，我们第一次证明了使用弹性蛋白样重组聚合物（ELR）工程化含有细胞粘附肽RGD可以导致具有高自我更新潜力的3D组织等效物，含有与天然组织本身一样多的增殖细胞。通过在纳米纤维ELR-胶原支架中共培养人固有层成纤维细胞和口腔上皮细胞来重建3D组织等效物。对这种口腔粘膜等同物的组织学、免疫组织学和透射电子显微镜分析表明，上皮细胞增殖（Ki 67）和分化（角蛋白13）特征性标志物的表达，以及多层上皮和表达层粘连蛋白332的超微结构组织良好的基底膜的存在。还证实了成纤维细胞合成新的细胞外基质。本文提出的支架具有很大的组织工程应用潜力，也可用于上皮细胞增殖和上皮细胞疾病（包括癌变）的研究。(C)2011爱思唯尔有限公司保留所有权利。
Three-dimensional epithelial tissue equivalents tend to lose their self-renewing potential progressively during culture as their epithelial cells lose their proliferative capacity with time. Even though the tissue engineered construct can mimic the native tissue well, it rapidly degrades after implantation due to the insufficient number of proliferating cells in the equivalent. In the present study we demonstrate for the first time that the use of an elastin-like recombinant polymer (ELR) engineered to contain the cell adhesion peptide RGD can result in a 3D tissue equivalent with high self-renewing potential, containing as many proliferative cells as the native tissue itself. The 3D tissue equivalent was reconstructed by the coculture of human lamina propria fibroblasts and oral epithelial cells in the nanofibrous ELR-collagen scaffold. Histological, immunohistological and transmission electron microscopic analyses of this oral mucosa equivalent demonstrated the expression of markers characteristic of epithelial proliferation (Ki67) and differentiation (keratin 13), and also the presence of a pluristratified epithelium and an ultrastructurally well-organized basement membrane expressing laminin 332. The synthesis of new extracellular matrix by the fibroblasts was also demonstrated. The scaffold proposed here presents great potential for tissue engineering applications, and also for studies of epithelial proliferation, and epithelial disorders including carcinogenesis. (C) 2011 Elsevier Ltd. All rights reserved.