A simple method to improve stem cell transplant therapy
Skeletal muscle stem cells (MuSCs) are an easily isolated population of adult stem cells that have been postulated as a therapy for inherited muscle disorders (including the muscular dystrophies), and a broad range of muscle injuries. To date, MuSC transplantation therapies have had limited success because of: 1) poor survival of transplanted cells; 2) lack of migration from the site of engraftment; and 3) an inability to integrate into the native niche environment. Importantly, these limitations can be overcome by preventing commitment to the myogenic lineage during ex vivo expansion. Dr. James Ryall recently characterised an exciting process of metabolic remodelling in MuSCs where a dramatic increase in glycolysis was found to regulate myogenic commitment.
In a series of follow-up experiments led by Dr Ryall with Professor Gordon Lynch, a range of ex vivo culture conditions have been characterised, where alterations in the extracellular environment induce a switch in metabolism and either prevent or delay the specification of MuSCs. These exciting data led to our working hypothesis that ex vivo metabolic remodelling of MuSCs will increase transplantation efficiency and improve skeletal muscle structure and function in models of injury and disease.
The results from this project will add to our fundamental understanding of the role of metabolism in regulating stem cell identity, and provide important information on a simple method to increase the viability of transplanted MuSCs.
See Dr James Ryall's own webpage.
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