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

该项目的主要科学目标是展示我们最近开发的人类子宫内膜支架的准确生理学，并建立这一新模型的能力，以支持由人、绒猴和小鼠多能干细胞创建的胚胎样模型的植入和早期发育。我们的愿景是，这种新的体外植入模型将颠覆在实验中使用动物来研究着床和早期胚胎发生的需要。这将实现该项目的3RS目标，并通过这样做将通过取代动物和减少研究中使用的动物数量来促进NC3R的使命。该项目的四个具体目标是：1)获得体外植入系统的人类胚胎发育的参考数据集，这将被用来对目标2和3.2中收集的数据进行基准测试)调查被称为胚泡的基于干细胞的人类胚胎模型在子宫内膜支架内发育的能力。3)确定由现有的小鼠和绒猴多能干细胞系制成的胚泡在人类子宫内膜支架系统中植入和发育的能力。4)创建一个全面的资源和培训计划，以最大限度地利用我们的新模型。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与生理相关的体外模型来研究胚胎着床和早期发育。在这里，我们将展示这个系统的准确性和重复性，我们将开发适当的方法，以确保这个无动物系统被其他研究人员广泛采用。更广泛地说，这种复杂的多组织人体细胞系统的成功建立将鼓励并提供一个框架，帮助开发其他体外模型来研究其他生理过程，这些生理过程可以取代动物在其他领域的使用。该项目很有可能成功，因为研究团队已经启动并运行了子宫内膜模型，从而完成了这项工作中风险最高的方面。两个研究小组距离很近，频繁的互动，以及主办机构世界级的培训和研究环境，共同支持了项目取得成功的可能性。

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.