PROBING THE MECHANICAL CONTROL OF STEM CELL FATE THROUGH THE DEVELOPMENT OF NOVEL, NON-INVASIVE IMAGING TECHNOLOGIES

尽管在我们日益老龄化的人口中，干细胞科学和技术在组织修复和再生方面有着巨大的希望，但由于一些明显的“障碍”，将这项技术应用到临床上的速度相对较慢。例如，虽然我们对实验室中干细胞的功能和反应知道很多，但我们对它们在个体组织中的行为知之甚少。另一个主要障碍是无法准确追踪细胞谱系并将它们与组织中的其他细胞类型区分开来(即当一个细胞分裂成两个细胞时，它们是相同的还是不同的？每次细胞分裂时，这种影响是相同的还是不同的？他们去了哪里？)。这项应用将通过将物理和生命科学中不同科学学科的研究人员聚集在一起，为干细胞科学开发新技术来解决这些问题。具体地说，我们将通过操纵细胞内的分子来开发非破坏性标记干细胞的新方法，这样我们就可以跟踪它们的位置和最终的命运(即这些干细胞变成了什么？)为了对细胞成像，我们将开发新的显微技术，使我们能够以非侵入性、无害的方式观察这些细胞(不同于目前的方法)，我们将利用最终使我们能够对患者组织深处的这些细胞进行成像的技术。能够跟踪这些干细胞将使我们能够检查它们周围组织环境的机械影响。有了这些知识，我们将机械地操纵周围环境，将干细胞引导到我们选择的组织中，以便按需提供定制设计的组织(无论是在实验室内，还是最终在患者体内)。总体而言，我们的最终目标是开发新的工具，使我们能够研究和控制干细胞生物学，以实现这些细胞的真正临床潜力。

Whilst in our increasing ageing population stem cell science and technology holds a great deal of promise within the context of tissue repair and regeneration, moving this technology to the clinics has been relatively slow due to a number of distinct 'barriers'. For example, whilst we know a lot about the function and response of stem cells in the laboratory, we know very little about their behaviour in tissues within individuals. A further major barrier has been the inability to accurately track cell lineages and to distinguish them from other cell types within the tissue (i.e. when one cell divides to become two cells are they the same or different? Is this effect the same or different each time the cell divides? Where do they go?). This application will address these issues by bringing together researchers across different scientific disciplines in the physical and life sciences to develop novel technologies for stem cell science. Specifically, we will develop new ways of non-destructively labelling stem cells by manipulating molecules within the cells so we can follow both their position and their eventual fate (i.e. what do these stem cells turn into?). In order to image the cells we will develop new microscopic techniques that allow us to view these cells in a non-invasive, non-harmful way (unlike current approaches) and we will utilise technologies that will eventually enable us to image these cells deep within patient tissues. Being able to follow these stem cells will allow us to examine the mechanical influence of their surrounding tissue environments. Armed with such knowledge we will mechanically manipulate the surrounding environment to direct stem cells into our tissue of choice in order to deliver custom designed tissues on demand (either within the laboratory or eventually within a patient). Overall, our ultimate aim is to develop new tools to allow us to investigate and control stem cell biology in order to realise the true clinical potential of these cells.