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.

骨骼和软骨的保养对健康的衰老至关重要。这些组织可能在骨关节炎等疾病中受到病理性干扰，或在意外损伤中受损，导致骨折不愈合。在这些情况下的治疗选择是有限的，因此，至关重要的是，进行研究，以开发新的治疗策略。人类干细胞生物学、基因编辑和三维细胞培养方面的最新技术进步意味着可以对可以在体内和病理环境中繁殖的原代人类细胞进行研究。我们实验室先前的工作已经确定了在新骨形成和软骨维持中起主要作用的途径。这提高了调节这些途径可用于治疗骨关节炎的病理学方面和/或在不愈合骨折的情况下增强骨折愈合的可能性。为了实现这一点，需要采取几个步骤。该研究项目将侧重于（a）使用重编程的人类诱导多能干细胞来产生骨和软骨生成所必需的细胞（例如成骨细胞和软骨细胞）（B）应用CRIPSr技术来遗传修饰途径，以便确定其治疗效用，以及（c）整合可控的3D凝胶来模拟组织环境。结合起来，这些研究将为人类骨生物学以及如何利用基于细胞的治疗方法来治疗/修复病理和意外损伤提供独特的见解。