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，并建立这种新模型的能力，以支持由人类，狨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推翻在实验中使用动物来研究植入和早期胚胎发生的需要。这将实现该项目的3Rs目标，并通过替代动物和减少用于研究的动物数量，为NC3Rs的使命做出贡献。该项目的四个具体目标是：1)获取体外植入系统中人类胚胎发育的参考数据集，用于对目标2和3.2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囊胚在子宫内膜支架内发育的能力。3)确定由现有小鼠和狨猴多能干细胞系制成的囊胚在人子宫内膜支架系统中植入和发育的能力。4)制定全面的资源和培训计划，以最大限度地利用我们的新模式。目前所有关于人类和其他物种胚胎植入和早期发育的研究都使用动物。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与生理相关的体外模型来研究胚胎植入和早期发育。在这里，我们将展示该系统的准确性和可重复性，我们将开发合适的方法来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，这些模型可以取代动物在其他领域的使用。该项目成功的可能性很大，因为研究小组已经建立并运行了子宫内膜模型，从而完成了这项工作中最危险的部分。两个研究团队的近距离接触、频繁的互动以及各自所在机构的世界级培训和研究环境共同支持了项目成功的可能性。