An engineered model of stem cell engraftment for skeletal muscle regeneration

EPSRC：Jacob Fleming：EP/N509516/1大多数受伤后的骨骼肌是高度和完全再生的。然而，在诸如肌营养不良症和严重创伤的疾病中，肌肉不能再生，并且肌肉在质量和数量上退化。肌肉包含一个独特的干细胞群体，称为卫星细胞，负责这种非凡的再生能力。这些细胞的正常功能依赖于它们所处的三维环境。因此，迄今为止，研究这些细胞必须依赖于动物模型。然而，组织工程学的进步已经允许创建工程化骨骼肌，其可能能够维持这种独特的干细胞群体。这样的模型将允许进行研究，例如高通量药物筛选，这在传统的动物模型中是不可能的。因此，该项目旨在将联合收割机工程化骨骼肌与新鲜分离的肌肉干细胞结合，以创建包含卫星细胞的工程化骨骼肌。该系统将允许对干细胞驱动的再生和干细胞植入进行建模，并且将成为寻找肌营养不良症和灾难性肌肉损伤的新型药物/治疗的有力工具。尝试该项目所需的技术由吉尔伯特实验室（加拿大）和刘易斯实验室（英国）共享，前者在分离和培养肌肉干细胞方面具有丰富的经验，后者在工程化骨骼肌和再生模型方面具有丰富的经验。正是出于这个原因，该项目旨在将这些专业知识结合起来，利用两个小组的互补经验，并创建一个在理解疾病和生理学方面具有应用的模型。

EPSRC : Jacob Fleming : EP/N509516/1 Skeletal muscle following the majority of injuries is highly and completely regenerative. However, in disorders such as muscular dystrophies and significant traumas muscle fails to regenerate, and muscle degrades in quality and quantity. Muscle contains a unique population of stem cells, called satellite cells, responsible for this remarkable regenerative capacity. The proper function of these cells relies on the three-dimensional environment in which they reside. For this reason studying these cells has to date relied upon animal models. However, advances in tissue engineering have allowed the creation of engineered skeletal muscles which may be capable of sustaining this unique stem cell population. Such models would allow studies to be performed, such as high throughput drug screens, which would not be possible in conventional animal models. This project therefore aims to combine engineered skeletal muscles in combination with freshly isolated muscle stem cells to create an engineered skeletal muscle containing satellite cells. This system will allow the modelling of stem cell driven regeneration and stem cell engraftment and would be a powerful tool in the search for novel drugs/treatments for muscular dystrophies and catastrophic muscle injuries. The technologies which are required to attempt this project are shared between the Gilbert Lab (Canada), who have significant experience isolating and culturing muscle stem cells, and the Lewis Lab (UK) which has established experience with engineered skeletal muscle and models of regeneration. It is for this reason that the project has been designed to bring together this expertise to exploit the complimentary experience of the two groups and create a model which has applications in understanding disease and physiology.