Role of Extracellular Matrix Biomolecules on Endometrial Epithelial Cell Attachment and Cytokeratin 18 Expression on Gelatin Hydrogels.

Role of Extracellular Matrix Biomolecules on Endometrial Epithelial Cell Attachment and Cytokeratin 18 Expression on Gelatin Hydrogels.
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DOI:
10.1021/acsbiomaterials.2c00247
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发表时间:
2022-09-12
影响因子:
5.8
通讯作者:
Harley, Brendan A. C.
Harley, Brendan A. C.
中科院分区:
工程技术2区
文献类型:
--
作者:
Zambuto, Samantha G.;Jain, Ishita;Clancy, Kathryn B. H.;Underhill, Gregory H.;Harley, Brendan A. C.

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子宫内膜在月经周期和妊娠期间的组织结构和组成发生深刻变化。子宫内膜细胞外基质(ECM)的动态重塑过程是子宫内膜稳态的主要因素,包括月经周期的变化。这种组织微环境的一个关键要素是子宫内膜基底膜,一种将子宫内膜上皮与下面的子宫内膜ECM分开的特殊蛋白质层。子宫内膜微环境的生物工程模型,提出了一个适当的子宫内膜ECM和基底膜可能提供一个改善的环境,研究子宫内膜上皮细胞(EEC)的功能。在这里,我们利用一个分层的方法,使用二维高通量微阵列和三维明胶水凝胶来定义模式的EEC附着和细胞角蛋白18(CK 18)的表达,在子宫内膜基底膜蛋白的组合。我们鉴定了促进增加EEC附着、增加CK 18强度或两者的组合(胶原IV +腱生蛋白C;胶原I +胶原III;透明质酸+腱生蛋白C;胶原V;胶原V +透明质酸;胶原III;和胶原I)。我们还确定了显着的EEC介导的重塑甲基丙烯酰胺功能化明胶基质环境通过分析新生蛋白质沉积。总之,我们报告的努力,以定制的定位基底膜相关蛋白和蛋白多糖,以研究子宫内膜微环境的组织工程模型。
The endometrium undergoes profound changes in tissue architecture and composition, both during the menstrual cycle as well as in the context of pregnancy. Dynamic remodeling processes of the endometrial extracellular matrix (ECM) are a major element of endometrial homeostasis, including changes across the menstrual cycle. A critical element of this tissue microenvironment is the endometrial basement membrane, a specialized layer of proteins that separates the endometrial epithelium from the underlying endometrial ECM. Bioengineering models of the endometrial microenvironment that present an appropriate endometrial ECM and basement membrane may provide an improved environment to study endometrial epithelial cell (EEC) function. Here, we exploit a tiered approach using two-dimensional high-throughput microarrays and three-dimensional gelatin hydrogels to define patterns of EEC attachment and cytokeratin 18 (CK18) expression in response to combinations of endometrial basement membrane proteins. We identify combinations (collagen IV + tenascin C; collagen I + collagen III; hyaluronic acid + tenascin C; collagen V; collagen V + hyaluronic acid; collagen III; and collagen I) that facilitate increased EEC attachment, increased CK18 intensity, or both. We also identify significant EEC mediated remodeling of the methacrylamide-functionalized gelatin matrix environment via analysis of nascent protein deposition. Together, we report efforts to tailor the localization of basement membrane-associated proteins and proteoglycans in order to investigate tissue-engineered models of the endometrial microenvironment.
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