Fully synthetic animal-free scaffolds: the future of sustainable and scalable organoid culture

全合成的无动物支架：可持续和可扩展的类器官培养的未来

• 批准号: 92486
• 金额: $ 14.41万
• 依托单位: MANCHESTER BIOGEL LIMITED
• 依托单位国家: 英国
• 项目类别: Collaborative R&D
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=92486
• 关键词: Fully; synthetic; animal; free; scaffolds

Organoids are 3-dimensional (3D) clusters of stem cells that come together and emulate the microenvironment within individual organs, whether that be liver, kidney, heart, gut or other specific organs. Essentially, they can be viewed as miniature, simplified organs. They typically range in size from a few micrometers to five millimeters and there are potentially as many different organoids as there are different tissues and organs in the body. Organoids can also be grown that mimic diseased such as cancer and brain disorders. Such a diverse range of organoids can form by controlling the differentiation of the specific stem cell used, which can be influenced by the cells receiving instructive signals from the 3D extracellular matrix (ECM) and its components, such as bioactive proteins, and the medium the organoids grow in.Organoids hold extraordinary promise: they are a truly disruptive technology capable of completely transforming our understanding of basic biology and also revolutionising the drug discovery process, and its reliance on animal models. That said, growing organoids in the laboratory still requires the use of animal-derived components; in particular, the 3D gel matrix in which organoids grow, which is made from mouse tumours. There are very few suppliers of this matrix and because it is made from animals, each batch is slightly different, it is also unusual in that it is liquid at 4oC but sets to a gel at room temperature, this makes it very difficult for scientists to use and not compatible with robotic systems needed in high throughput drug discovery. Thus, to fully develop the potential of organoids in their capacity to reduce the need for use of animals in research, it is essential that a replacement for this type of 3D matrix is obtained, which is not derived from animals. The aim of this project is to develop a new, fully synthetic (non-animal derived) 3D gel matrix which is optimised for the growth of organoids and can be used in the future for industrial-scale organoid production to drive forwards biomedical research, drug discovery and development of new therapeutics. This will be achieved by combining the proprietary synthetic matrix from Manchester BIOGEL with the optimised bioactive cell signalling growth factor proteins from Qkine to create a wholly synthetic hydrogel that recreates the ideal growth environment for the organoids. Cellesce, a specialist organoid company will help tailor the synthetic hydrogels for different organoid types and downstream applications to maximise the impact on science and the commercial potential of the combined technology.

类器官是干细胞的三维（3D）簇，它们聚集在一起并模拟单个器官内的微环境，无论是肝脏，肾脏，心脏，肠道还是其他特定器官。从本质上讲，它们可以被看作是微型的、简化的器官。它们的大小通常从几微米到五毫米不等，并且可能有许多不同的类器官，因为体内有不同的组织和器官。类器官也可以模拟癌症和脑部疾病等疾病。通过控制所使用的特定干细胞的分化可以形成如此多样化的类器官，这可以受到细胞从3D细胞外基质（ECM）及其组分（如生物活性蛋白）接收指导信号的影响，以及类器官生长的培养基。类器官具有非凡的前景：它们是一种真正具有颠覆性的技术，能够彻底改变我们对基础生物学的理解，并彻底改变药物发现过程及其对动物模型的依赖。也就是说，在实验室中生长类器官仍然需要使用动物源性成分;特别是类器官生长的3D凝胶基质，它由小鼠肿瘤制成。这种基质的供应商很少，因为它是由动物制成的，每批略有不同，它在4 ℃下是液体，但在室温下凝固成凝胶，这也是不寻常的，这使得科学家很难使用，并且与高通量药物发现所需的机器人系统不兼容。因此，为了充分开发类器官的潜力，以减少在研究中使用动物的需要，获得这种类型的3D基质的替代品是至关重要的，它不是来自动物。该项目的目的是开发一种新的全合成（非动物源性）3D凝胶基质，该基质针对类器官的生长进行了优化，并可在未来用于工业规模的类器官生产，以推动生物医学研究，药物发现和新疗法的开发。这将通过将曼彻斯特BIOGEL的专有合成基质与Qkine的优化生物活性细胞信号传导生长因子蛋白相结合来实现，以创建一种完全合成的水凝胶，为类器官重建理想的生长环境。Cellesce是一家专业的类器官公司，它将帮助为不同的类器官类型和下游应用定制合成水凝胶，以最大限度地发挥组合技术对科学和商业潜力的影响。