An engineered model of stem cell engraftment for skeletal muscle regeneration

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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.