Novel in vitro endometrial scaffolds to investigate embryo implantation and early development

该项目的首要科学目标是证明我们最近开发的人类子宫内膜支架的准确生理学，并建立这种新模型支持人类胚胎样模型的植入和早期发育的能力，我们的愿景是，这种新的体外植入模型将推翻在实验中使用动物进行研究的必要性。着床和早期胚胎发生。这将实现本项目的3R目标，并通过替代动物和减少研究中使用的动物数量，为NC3R的使命做出贡献。本项目的四个具体目标是：1）获得体外植入系统人类胚胎发育的参考数据集，其将用于对目标2和3.2）中收集的数据进行基准测试。2）研究基于干细胞的人类胚胎模型（称为类胚细胞）在子宫内膜支架内发育的能力。3）确定由现有小鼠和绒猴多能干细胞系制成的类胚体在人子宫内膜支架系统中植入和发育的能力。创建一个全面的资源和培训计划，以最大限度地提高我们的新模型的吸收。目前所有关于人类胚胎植入和早期发育的研究，其他物种使用动物。这是因为没有合适的体外模型可以提供更好的替代方法来研究这些关键过程。我们的项目很重要，因为它将提供第一个生理相关的体外模型来研究胚胎植入和早期发育。在这里，我们将证明该系统的准确性和可重复性，并将开发适当的方法，以确保其他研究人员广泛采用这种无动物系统。更广泛地说，这种复杂的、多组织的人类细胞系统的成功建立将鼓励并提供一个框架，以帮助开发其他体外模型来研究其他生理过程，这些过程可以在其他领域取代动物。该项目成功的机会很高，因为研究团队已经建立了子宫内膜模型并运行，从而完成工作中最危险的部分。两个研究团队的紧密联系，他们频繁的互动，以及他们所在机构的世界级培训和研究环境，共同支持项目成功的可能性。

The overarching scientific goals of this project are to demonstrate the accurate physiology of human endometrial scaffolds that we have recently developed, and to establish the ability of this new model to support the implantation and early development of embryo-like models created from human, marmoset and mouse pluripotent stem cells.Our vision is that this new in vitro implantation model will overturn the need to use animals in experiments to study implantation and early embryogenesis. This will achieve the 3Rs goal of this project and in doing so will contribute to the mission of the NC3Rs by replacing animals and reducing the number of animals used in research.The four specific objectives of this project are:1) Obtain reference data sets of human embryo development with the in vitro implantation system, which will be used to benchmark the data collected in Objectives 2 and 3.2) Investigate the ability of stem cell-based human embryo models called blastoids to develop within the endometrial scaffold.3) Determine the ability of blastoids made from existing mouse and marmoset pluripotent stem cell lines to implant and develop in the human endometrial scaffold system.4) Create a comprehensive resource and training programme to maximise the uptake of our new models.All current studies on embryo implantation and early development in humans and other species use animals. This is because there are no suitable in vitro models that can provide a better, alternative approach to investigate these key processes. Our project is important because it will provide the first physiologically-relevant in vitro model to study embryo implantation and early development. Here, we will demonstrate the accuracy and reproducibility of this system and we will develop suitable means to ensure the broad uptake of this animal-free system to other researchers. More generally, the successful establishment of this complex, multi-tissue human cellular system will encourage and provide a framework to help the development of other in vitro models to study additional physiological processes that could replace the use of animal in those other fields.The project has a high chance to succeed because the research team already have the endometrial model up and running, thereby completing the riskiest aspect of the work. The close physical proximity of the two research teams, their frequent interactions, and the world-class training and research environments of their host institutes collectively support the likelihood of a successful project outcome.