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

保持骨骼和软骨对健康衰老是必不可少的。这些组织可能在骨关节炎等疾病中受到病理干扰，或者在意外受伤时受到损害，导致骨不连骨折。在这些环境下的治疗选择是有限的，因此开展研究以开发新的治疗策略是至关重要的。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，有可能对能够在体内和病理环境中繁殖的原代人类细胞进行研究。我们实验室之前的工作已经确定了在新骨形成和软骨维护中发挥主要作用的途径。这增加了这些通路的调节可用于治疗骨关节炎的病理方面和/或在骨不连骨折病例中增强骨折愈合的可能性。为了实现这一目标，需要采取几个步骤。这项研究将侧重于(A)使用重新编程的人类诱导多能干细胞来生成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技术对途径进行基因修改，以便确定其治疗效果，以及(C)集成可控制的3D凝胶来模拟组织环境。结合起来，这些研究将为人类骨骼生物学以及如何利用基于细胞的疗法来治疗/修复病理和意外损伤提供独特的见解。

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.