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一种器官型组织工程化人食管黏膜模型的开发和表征。

The development and characterization of an organotypic tissue-engineered human esophageal mucosal model.

机构信息

Department of Engineering Materials, Kroto Research Institute, University of Sheffield, Sheffield, United Kingdom.

出版信息

Tissue Eng Part A. 2010 Mar;16(3):1053-64. doi: 10.1089/ten.TEA.2009.0217.

DOI:10.1089/ten.TEA.2009.0217
PMID:19845463
Abstract

There is a demand for a reliable three-dimensional tissue-engineered model of the esophageal mucosa for use as an experimental platform for investigating esophageal epithelial biology and the pathogenesis of esophageal neoplasia and precursor lesions such as Barrett's metaplasia. A number of models have been described, but there has been little systematic assessment of the different approaches, making selection of a preferred platform difficult. This study assesses the properties of organotypic cultures using four different scaffolds (human esophageal matrix, porcine esophageal matrix, human dermal matrix, and collagen) and two different epithelial cell types (primary human esophageal squamous cells and the Het-1A esophageal squamous cell line). Human esophageal matrix and dermis did not give consistent results, but porcine esophageal matrix and collagen proved more reliable and were studied in greater detail. Both matrices supported the formation of a mature stratified epithelium that was similar to that of the normal human esophagus, demonstrated by Ki67, CK4, CK14, and involucrin staining. However, collagen showed reduced epithelial adherence, while fibroblast penetration into the porcine matrix was poor. Composite cultures using Het-1A cells formed a hyperproliferative epithelium with no evidence of differentiation. We propose human esophageal squamous cells seeded onto porcine esophageal matrix as the preferred model of the normal human esophagus.

摘要

人们需要一个可靠的三维组织工程食管黏膜模型,用作研究食管上皮生物学和食管肿瘤发生以及巴雷特化生等前体病变的发病机制的实验平台。已经描述了许多模型,但对不同方法的系统评估很少,使得选择首选平台变得困难。本研究使用四种不同的支架(人食管基质、猪食管基质、人真皮基质和胶原)和两种不同的上皮细胞类型(原代人食管鳞状细胞和 Het-1A 食管鳞状细胞系)评估了器官型培养物的特性。人食管基质和真皮基质没有给出一致的结果,但猪食管基质和胶原证明更可靠,并进行了更详细的研究。两种基质都支持形成类似于正常人体食管的成熟分层上皮,通过 Ki67、CK4、CK14 和兜甲蛋白染色证明。然而,胶原显示出上皮附着减少,而猪基质中的成纤维细胞渗透不良。使用 Het-1A 细胞的复合培养形成了一种无分化证据的过度增殖上皮。我们建议将人食管鳞状细胞接种到猪食管基质上作为正常人体食管的首选模型。

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