Reprogramming of induced pluripotent stem cells to 3D model bone and cartilage formation

将诱导多能干细胞重编程为 3D 模型骨和软骨形成

• 批准号: 2284928
• 金额: --
• 依托单位: University of Glasgow
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2284928
• 关键词: Reprogramming; induced; pluripotent; stem; cells

Maintenace of bone and cartilage is essential for healthy ageing. These tissues can be pathologically perturbed in diseases such as osteoarthritis or compromised in accidental injury leading to non-union fractures. Therapeutic options in these settings are limited and it is therefore paramount that studies are undertaken to develop new therapeutic strategies. Recent technological advances in human stem biology, genetic editing and 3-dimensional cell culture, means that it possible to undertake studies with primary human cells that can reproduce in vivo and pathological settings. Prior work in our laboratory has identified pathways that play major roles in new bone formation and cartilage maintenance. This raises the possibility that modulation of these pathways can be used to treat pathological aspects of osteoarthritis and/or enhance fracture healing in cases of non-union fractures. In order to achieve this, several steps need to be undertaken. This studentship will focus on (a) using reprogrammed human induced pluripotent stem cells to generate cells essential for bone and cartilage generation (e.g. osteoblasts and chondrocytes) (b) applying CRIPSr technology to genetically modify pathways so their therapeutic utility can be determined and (c) integrating controllable 3D gels to model tissue environments. Combined, these studies will provide unique insights into human bone biology and how cell-based therapeutics can be harnessed to treat/repair pathological and accidental damage.

骨骼和软骨的维护对于健康衰老至关重要。这些组织在诸如骨关节炎等疾病中可能会受到病理的干扰，也可能在导致非工会骨折的意外损伤中受到损害。这些环境中的治疗选择是有限的，因此至关重要的是进行研究以制定新的治疗策略。人类干生物学，遗传编辑和三维细胞培养的最新技术进步意味着可以对可以在体内和病理环境中再现的原代人细胞进行研究。我们实验室的先前工作已经确定了在新的骨形成和软骨维护中起着重要作用的途径。这增加了这些途径的调节可以用于治疗骨关节炎的病理方面和/或在非工会骨折的情况下增强骨折愈合。为了实现这一目标，需要采取几个步骤。该学生将重点介绍（a）使用重编程的人类诱导的多能干细胞来产生对骨骼和软骨产生必不可少的细胞（例如，成骨细胞和软骨细胞）（b）将CRIPSR技术应用于遗传修饰的途径，以使其治疗效率可以确定，并确定其治疗效率，并确定（c）可控制的3DDD凝胶，以模拟3D凝胶。这些研究结合在一起，将提供对人骨生物学的独特见解，以及如何利用基于细胞的治疗剂来治疗/修复病理和意外损害。