Zambuto Samantha G, Clancy Kathryn B H, Harley Brendan A C
Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Department of Anthropology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Interface Focus. 2019 Oct 6;9(5):20190016. doi: 10.1098/rsfs.2019.0016. Epub 2019 Aug 16.
The endometrium is the lining of the uterus and site of blastocyst implantation. Each menstrual cycle, the endometrium cycles through rapid phases of growth, remodelling and breakdown. Significant vascular remodelling is also driven by trophoblast cells that form the outer layer of the blastocyst. Trophoblast invasion and remodelling enhance blood flow to the embryo ahead of placentation. Understanding the mechanisms of endometrial vascular remodelling and trophoblast invasion would provide key insights into endometrial physiology and cellular interactions critical for establishment of pregnancy. The objective of this study was to develop a tissue engineering platform to investigate the processes of endometrial angiogenesis and trophoblast invasion in a three-dimensional environment. We report adaptation of a methacrylamide-functionalized gelatin hydrogel that presents matrix stiffness in the range of the native tissue, supports the formation of endometrial endothelial cell networks with human umbilical vein endothelial cells and human endometrial stromal cells as an artificial endometrial perivascular niche and the culture of an endometrial epithelial cell layer, enables culture of a hormone-responsive stromal compartment and provides the capacity to monitor the kinetics of trophoblast invasion. With these studies, we provide a series of techniques that will instruct researchers in the development of endometrial models of increasing complexity.
子宫内膜是子宫的内衬，也是囊胚着床的部位。每个月经周期，子宫内膜都会经历快速的生长、重塑和分解阶段。滋养层细胞（构成囊胚外层）也驱动着显著的血管重塑。在胎盘形成之前，滋养层的侵袭和重塑会增加流向胚胎的血流量。了解子宫内膜血管重塑和滋养层侵袭的机制，将为子宫内膜生理学以及对妊娠建立至关重要的细胞相互作用提供关键见解。本研究的目的是开发一个组织工程平台，以研究三维环境下子宫内膜血管生成和滋养层侵袭的过程。我们报告了一种甲基丙烯酰胺功能化明胶水凝胶的应用，该水凝胶具有与天然组织相当的基质硬度，能支持人脐静脉内皮细胞和人子宫内膜基质细胞形成子宫内膜内皮细胞网络，作为人工子宫内膜血管周围微环境并培养子宫内膜上皮细胞层，能培养对激素有反应的基质隔室，并具备监测滋养层侵袭动力学的能力。通过这些研究，我们提供了一系列技术，将指导研究人员开发复杂性不断增加的子宫内膜模型。
