Supervised morphogenesis in gastruloids

原肠胚中受监督的形态发生

• 批准号: 10050213
• 金额: $ 84.51万
• 依托单位: UNIVERSITY OF GLASGOW
• 依托单位国家: 英国
• 项目类别: EU-Funded
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=10050213
• 关键词: Supervised; morphogenesis; gastruloids

The lack of realistic in vitro organ models that can faithfully represent in vivo physiological processes is a major obstacle affecting the biological and medical sciences. The current gold standard is animal experiments, but it is increasingly clear that these models mostly fail to recapitulate the human physiology. Moreover, animal experiments are controversial, and it is a common goal in the scientific community to minimize the use of animals to a strictly necessary minimum. The emergence of stem cell engineered organ models called organoids represents the only viable alternative to animal research. However, current organoid technology is yet to produce the larger physiologically relevant organ models that the medical sciences really need. Specifically, current organoids are too small, not vascularized and lack the 3-dimensional organization found in vivo. In this interdisciplinary project we aim to challenge all these limitations by using the recently developed gastruloid technology guided by cutting edge bioengineering and artificial intelligence. Gastruloids are formed by initiating the very early developmental processes and develops along a highly coordinated three axial process that closely resembles mammalian embryogenesis. Moreover, gastruloids can develop several organ precursors simultaneously and thus constitutes important improvements over conventional single-tissue organoids. To harvest the potential of gastruloid technology we will first implement large sequencing and imaging experiments to optimize the developmental trajectory of gastruloids for organ inductions. We will then build these datasets into a multimodal data matrix to identify gastruloid candidates for cardiovascular and foregut development. Specifically, we will identify candidates that show strong vasculogenesis as candidates for later vascularisation by anastomose with endothelial cells.

缺乏真实的体外器官模型，可以忠实地代表在体内的生理过程是影响生物和医学科学的主要障碍。目前的黄金标准是动物实验，但越来越清楚的是，这些模型大多无法概括人类生理学。此外，动物实验是有争议的，科学界的共同目标是将动物的使用减少到严格必要的最低限度。被称为类器官的干细胞工程器官模型的出现代表了动物研究的唯一可行替代方案。然而，目前的类器官技术尚未产生医学科学真正需要的更大的生理相关器官模型。具体来说，目前的类器官太小，没有血管化，缺乏体内发现的三维组织。在这个跨学科的项目中，我们的目标是通过使用最新开发的gastruloid技术来挑战所有这些限制，该技术由尖端生物工程和人工智能指导。类胃腺是由非常早期的发育过程开始形成的，并沿着沿着高度协调的三轴过程发育，非常类似于哺乳动物的胚胎发生。此外，类胃体可以同时发育几个器官前体，因此构成了对传统单组织类器官的重要改进。为了挖掘类胃体技术的潜力，我们将首先实施大型测序和成像实验，以优化类胃体的发育轨迹，用于器官诱导。然后，我们将这些数据集构建成多模态数据矩阵，以识别心血管和前肠发育的胃样候选物。具体来说，我们将确定候选人，显示出强大的血管生成的候选人，为以后的血管化与内皮细胞的蔗糖。