Characterising embryonic stem cell-derived tenocytes and defining the changing role of scleraxis during tendon development

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Theme: Bioscience for HealthTo aid adult tendon regeneration and reduce the frequency of re-injury novel strategies are being developed which use stem cells that have the potential to differentiate into tenocytes. However, during normal adult tendon repair there is already a substantial influx of tenocytes which produce scar tissue. It is therefore important to design cell therapies that can mimic fetal tenocytes and recapitulate scar-less regeneration. We have shown that equine ESCs differentiate into tenocytes following their injection into the injured horse tendon. Using an in vitro 3D culture system to generate artificial tendons, we have identified transforming growth factor beta 3 and mechanical force as key drivers of differentiation. However, whether ESC-derived tenocytes represent adult or fetal cells is unknown. In this PhD the student will exploit new ways of working by performing global gene expression analyses on ESC-derived, adult and fetal tenocytes. Bioinformatics approaches will be used to determine the developmental stage that ESC-tenocytes represent. Global gene expression analyses will also be performed on cells that are engineered to have knocked down scleraxis levels to identify genes that are downstream of scleraxis regulation. Our synthetic cell culture system to generate artificial tendons will be used and the student will have the opportunity to refine this model by employing bioengineering techniques to apply forces to the tendons to better mimic the in vivo situation. The results of this project will provide novel information to inform future experimental and clinical studies on the application of cell based-therapies for modulating tendon regeneration. ENWW:- data driven biology (bioinformatics)- global gene expression analyses- biological imaging of cells - synthetic biology (3D culture, cell genetic engineering)- statistical analysis of various experimental data