Bioengineering of human intestinal stem cells and organoid 3D culture systems for tissue regeneration and drug discovery

在健康的肠道中，上皮组织的稳态是由一群具有多能性和自我更新的成体干细胞支撑的。成体干细胞还可以再生受损组织，以应对细胞应激，从而恢复器官稳态和预防疾病。因此，有强烈的兴趣，了解分子，生物化学，细胞和机械调节的成体干细胞。3D类器官培养系统的出现有望为干细胞生物学的调控提供独特的见解。该项目旨在开发完全定义的合成和可优化的微凝胶系统，用于培养肠道干细胞并扩展为3D培养的类器官。该系统将用于研究机械转导和生化信号对肠道干细胞生物学和3D类器官发育的性质和影响。 该项目建立在最近内部成功制造微珠和开发新型纤维素水凝胶和肠道3D类器官培养系统的基础上。

In a healthy gut, epithelial tissue homeostasis is underpinned by a population of adult stem cells that possess multipotency and self-renewal. Adult stem cells can also regenerate damaged tissues in response to cellular stress thereby restoring organ homeostasis and preventing disease. Hence, there is intense interest in understanding the molecular, biochemical, cellular and mechanical regulation of adult stem cells. The emergence of 3D organoid culture systems promises unique insights into the regulation of stem cell biology. This project aims to develop fully-defined synthetic and optimisable microgel systems for the culture of intestinal stem cells and expansion into 3D cultured organoids. This system will be used to investigate the nature and influence of mechanotransduction and biochemical signals on intestinal stem cell biology and the development of the 3D organoids. This project builds on recent in-house successes in the fabrication of microbeads and the development of novel cellulose-based hydrogels and intestinal 3D organoid culture system.