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

用于研究胚胎植入和早期发育的新型体外子宫内膜支架

• 批准号: NC/Y500550/1
• 金额: $ 17.2万
• 依托单位: Babraham Institute
• 依托单位国家: 英国
• 项目类别: Training Grant
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=NC%2FY500550%2F1
• 关键词: Novel; vitro; endometrial; scaffolds; investigate

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.

该项目的总体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，并建立了这种新模型支持植入和早期开发胚胎型模型的植入和早期开发的能力，这些模型由人，摩尔莫斯和鼠标和鼠标鼠类多型干细胞产生。这将实现该项目的3RS目标，这样做将通过更换动物并减少研究中使用的动物数量来为NC3RS的使命做出贡献。该项目的四个特定目标是：1）获得人类胚胎开发的参考数据集，并使用体外植入系统，该系统将用于在人类中构建的胚胎中的数据，该数据将在该模型中播放，该模型将在该模型中播放到词汇中，该词汇在3.2和3.2中的数据中所收集的数据，该系统将在3.2和3.2中）。3。2和3.2）子宫内膜支架。3）确定由现有的小鼠和摩尔果多能干细胞系制成的类胚型植入物的能力，并在人体子宫内膜支架系统中发展并发展。4）创建一个全面的资源和培训计划，以最大程度地吸收我们的新模型。所有有关人类植入和早期在人类和其他物种中使用动物的研究。这是因为没有合适的体外模型可以提供更好的，替代的方法来研究这些关键过程。我们的项目很重要，因为它将为研究胚胎植入和早期发育提供第一个与生理上的体外模型。在这里，我们将证明该系统的准确性和可重复性，我们将开发合适的手段，以确保对其他研究人员广泛吸收这种无动物的系统。更一般地，成功建立了这个复杂的多组织人类细胞系统将鼓励并提供一个框架，以帮助开发其他体外模型，以研究其他生理过程，这些过程可以取代其他领域中的动物使用。该项目很有可能成功，因为研究团队已经具有子宫内膜模型，从而完成了工作，从而完成了工作最风险的工作。两个研究团队的近距离接近，他们的频繁互动以及其主人研究所的世界一流的培训和研究环境共同支持成功的项目成果的可能性。