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一种用于改善当前人类模型及未来应用的天然异种子宫内膜细胞外基质水凝胶

A Natural Xenogeneic Endometrial Extracellular Matrix Hydrogel Toward Improving Current Human Models and Future Applications.

作者信息

López-Martínez Sara, Campo Hannes, de Miguel-Gómez Lucía, Faus Amparo, Navarro Alfredo T, Díaz Ana, Pellicer Antonio, Ferrero Hortensia, Cervelló Irene

机构信息

Fundación Instituto Valenciano de Infertilidad, Instituto de Investigación Sanitaria La Fe, Valencia, Spain.

University of Valencia, Valencia, Spain.

出版信息

Front Bioeng Biotechnol. 2021 Mar 5;9:639688. doi: 10.3389/fbioe.2021.639688. eCollection 2021.

DOI:10.3389/fbioe.2021.639688
PMID:33748086
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7973233/
Abstract

Decellularization techniques support the creation of biocompatible extracellular matrix hydrogels, providing tissue-specific environments for both cell culture and tissue regeneration. We obtained endometrium derived from porcine decellularized uteri to create endometrial extracellular matrix (EndoECM) hydrogels. After decellularization and detergent removal, we investigated the physicochemical features of the EndoECM, including gelation kinetics, ultrastructure, and proteomic profile. The matrisome showed conservation of structural and tissue-specific components with low amounts of immunoreactive molecules. EndoECM supported culture of human endometrial cells in two- and three-dimensional conditions and improved proliferation of endometrial stem cells with respect to collagen and Matrigel. Further, we developed a three-dimensional endometrium-like co-culture system of epithelial and stromal cells from different origins. Endometrial co-cultures remained viable and showed significant remodeling. Finally, EndoECM was injected subcutaneously in immunocompetent mice in a preliminary study to test a possible hypoimmunogenic reaction. Biomimetic endometrial milieus offer new strategies in reproductive techniques and endometrial repair and our findings demonstrate that EndoECM has potential for endometrial culture and as treatment for endometrial pathologies.

摘要

去细胞技术有助于制备生物相容性细胞外基质水凝胶，为细胞培养和组织再生提供组织特异性环境。我们从猪去细胞子宫中获取子宫内膜，以制备子宫内膜细胞外基质（EndoECM）水凝胶。在去细胞和去除去污剂后，我们研究了EndoECM的物理化学特性，包括凝胶化动力学、超微结构和蛋白质组学特征。基质组显示结构和组织特异性成分得以保留，免疫反应性分子含量较低。EndoECM支持人子宫内膜细胞在二维和三维条件下培养，并相对于胶原蛋白和基质胶促进了子宫内膜干细胞的增殖。此外，我们构建了一个由不同来源的上皮细胞和基质细胞组成的三维类子宫内膜共培养系统。子宫内膜共培养物保持活力并显示出显著的重塑。最后，在一项初步研究中，将EndoECM皮下注射到具有免疫活性的小鼠体内，以测试可能的低免疫原性反应。仿生子宫内膜环境为生殖技术和子宫内膜修复提供了新策略，我们的研究结果表明，EndoECM在子宫内膜培养和子宫内膜疾病治疗方面具有潜力。

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